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At least 163 records · Page 9Linked to original sources
PubMed2003

Mediolateral reaction forces and forelimb anatomy in quadrupedal primates: implications for interpreting locomotor behavior in fossil primates.

The forelimb joints of terrestrial primate quadrupeds appear better able to resist mediolateral (ML) shear forces than those of arboreal quadrupedal monkeys. These differences in forelimb morphology have been used extensively to infer locomotor behavior in extinct primate quadrupeds. However, the nature of ML substrate reaction forces (SRF) during arboreal and terrestrial quadrupedalism in primates is not known. This study documents ML-SRF magnitude and orientation and forelimb joint angles in six quadrupedal anthropoid species walking across a force platform attached to terrestrial (wooden runway) and arboreal supports (raised horizontal poles). On the ground all subjects applied a lateral force in more than 50% of the steps collected. On horizontal poles, in contrast, all subjects applied a medially directed force to the substrate in more than 75% of the steps collected. In addition, all subjects on arboreal supports combined a lower magnitude peak ML-SRF with a change in the timing of the ML-SRF peak force. As a result, during quadrupedalism on the poles the overall SRF resultant was relatively lower than it was on the runway. Most subjects in this study adduct their humerus while on the poles. The kinetic and kinematic variables combine to minimize the tendency to collapse or translate forelimbs joints in an ML plane in primarily arboreal quadrupedal primates compared to primarily terrestrial quadrupedal ones. These data allow for a more complete understanding of the anatomy of the forelimb in terrestrial vs. arboreal quadrupedal primates. A better understanding of the mechanical basis of morphological differences allows greater confidence in inferences concerning the locomotion of extinct primate quadrupeds.

Animals↗
PubMed2003

Tbx5 is required for forelimb bud formation and continued outgrowth.

Tbx5 is a T-box transcription factor expressed exclusively in the developing forelimb but not in the developing hindlimb of vertebrates. Tbx5 is first detected in the prospective forelimb mesenchyme prior to overt limb bud outgrowth and its expression is maintained throughout later limb development stages. Direct evidence for a role of Tbx5 in forelimb development was provided by the discovery that mutations in human TBX5 cause Holt-Oram Syndrome (HOS), a dominant disorder characterised predominantly by upper(fore) limb defects and heart abnormalities. Misexpression studies in the chick have demonstrated a role for this gene in limb-type specification. Using a conditional knockout strategy in the mouse to delete Tbx5 gene function in the developing forelimb, we demonstrate that this gene is also required at early limb bud stages for forelimb bud development. In addition, by misexpressing dominant-negative and dominant-activated forms of Tbx5 in the chick wing we provide evidence that this gene is also required at later stages of limb bud development for continued limb outgrowth. Our results provide a context to understand the defects observed in HOS caused by haploinsufficiency of TBX5 in human. Moreover, our results also demonstrate that limb bud outgrowth and specification of limb identity are linked by a requirement for Tbx5.

Animals↗
PubMed2001

Consistent features in the forelimb representation of primary motor cortex in rhesus macaques.

The purpose of this study was to systematically map the forelimb area of primary motor cortex (M1) in rhesus macaques in an effort to investigate further the organization of motor output to distal and proximal muscles. We used stimulus-triggered averaging (StTAing) of electromyographic activity to map the cortical representation of 24 simultaneously recorded forelimb muscles. StTAs were obtained by applying 15 microA stimuli to M1 sites while the monkey performed a reach and prehension task. Motor output to body regions other than the forelimb (e.g., face, trunk, and hindlimb) was identified using repetitive intracortical microstimulation to evoke movements. Detailed, muscle-based maps of M1 revealed a central core of distal (wrist, digit, and intrinsic hand) muscle representation surrounded by a "horseshoe"-shaped zone of proximal (shoulder and elbow) muscle representation. The core distal and proximal zones were separated by a relatively large region representing combinations of both distal and proximal muscles. On the basis of its size and characteristics, we argue that this zone is not simply the result of stimulus-current spread, but rather a distinct zone within the forelimb representation containing cells that specify functional synergies of distal and proximal muscles. Electrode tracks extending medially from the medial arm of the proximal muscle representation evoked trunk and hindlimb responses. No distal or proximal muscle poststimulus effects were found in this region. These results argue against the existence of a second, major noncontiguous distal or proximal forelimb representation located medially within the macaque M1 representation.

Animals↗
PubMed1985

Response of the forelimb vasculature to vasoactive agents: effects of ouabain.

The effect of the local intra-arterial infusion of ouabain (11.8 micrograms/min.) on the response of the forelimb to vasoactive agents was examined. In seven dogs, bolus injections of CaCl2, MgSO4, KCl, norepinephrine, adenosine, acetylcholine, PGE1 and saline were made into the forelimb perfused at constant flow before and three times during ouabain infusion. Ouabain blocked potassium vasodilation and changed the response to CaCl2 from vasoconstriction to vasodilation. The response of the forelimb to the other vasoactive agents was initially unaffected by ouabain but with time the forelimb vasculature became less sensitive to all agents studied. These changes were not seen in a series of 5 saline infused control animals. In a third series of animals steady-state dose responses to CaCl2, Ca-gluconate and KCl were explored by infusing solutions intrabrachially at three dosages. Before ouabain, forelimb resistance increased as a function of Ca++ and decreased as a function of K+. Ouabain completely blocked potassium vasodilation and on the average blocked Ca++ vasoconstriction although a number of animals evidenced vasodilation to Ca++ during ouabain infusion. These data indicate that K+ vasodilation is Na+, K+-ATPase dependent and that Na+, K+-ATPase inhibition unmasks a vasodilatory action of locally applied Ca++.

Alprostadil↗
PubMed1984

Effects of dopamine (DA) and SKF 82526, a selective DA1-receptor agonist, on vascular resistances in the canine forelimb.

This study was performed to determine the presence of vascular dopamine (DA1) receptors in the canine forelimb. Local i.a. infusions of DA (2, 4 or 8 micrograms base/min) produced cutaneous and skeletal muscle vasoconstriction in the forelimb comparable to that produced by local i.a. infusions of norepinephrine (0.5, 1 or 4 micrograms base/min). In the cutaneous vasculature, DA produced large artery, small vessel and large vein constrictions. The small vessels and large veins constricted proportionately more than the large arteries. The pattern of constriction produced by DA along the cutaneous vascular tree was similar to that produced by norepinephrine. The forelimb vasoconstriction produced by both DA and norepinephrine was abolished completely by treatment with phentolamine, indicating that both agents produce vasoconstriction mediated by stimulation of alpha adrenoceptors. The failure of DA to produce vasodilation after phentolamine suggests that there are no vascular or DA1-subtype DA receptors in the canine forelimb vasculature. The local i.a. infusion of SKF 82526, a selective DA1-receptor agonist, for 3 min produced cutaneous and skeletal muscle dilation which could be antagonized by either sulpiride or phentolamine. This neurogenic dopaminergic vasodilation produced by SKF 82526 (25, 50 or 100 micrograms base/min) was converted into vasoconstriction after ganglionic blockade. Inasmuch as SKF 82526 does not activate presynaptic or DA2-subtype DA receptors, the neurogenic vasodilation caused by SKF 82526 may be due to a dopaminergic inhibition of ganglionic transmission. Whereas the results of our study fail to provide any evidence for the presence of vascular DA (DA1) receptors in the canine forelimb, they show that SKF 82526, a DA1-receptor agonist, produces neurogenic vasodilation probably by activating ganglionic DA receptors.

Animals↗
PubMed2000

Cineradiographic study of forelimb movements during quadrupedal walking in the brown lemur (Eulemur fulvus, Primates: Lemuridae).

Movements of forelimb joints and segments during walking in the brown lemur (Eulemur fulvus) were analyzed using cineradiography (150 frames/sec). Metric gait parameters, forelimb kinematics, and intralimb coordination are described. Calculation of contribution of segment displacements to stance propulsion shows that scapular retroversion in a fulcrum near the vertebral border causes more than 60% of propulsion. The contribution by the shoulder joint is 30%, elbow joint 5%, and wrist joint 1%. Correlation analysis was applied to reveal the interdependency between metric and kinematic parameters. Only the effective angular movement of the elbow joint during stance is speed-dependent. Movements of all other forelimb joints and segments are independent of speed and influence, mainly, linear gait parameters (stride length, stance length). Perhaps the most important result is the hitherto unknown and unexpected degree of scapular mobility. Scapular movements consist of ante-/retroversion, adduction/abduction, and scapular rotation about the longitudinal axis. Inside rotation of the scapula (60 degrees -70 degrees ), together with flexion in the shoulder joint, mediates abduction of the humerus, which is not achieved in the shoulder joint, and is therefore strikingly different from humeral abduction in man. Movements of the shoulder joint are restricted to flexion and extension. At touch down, the shoulder joint of the brown lemur is more extended compared to that of other small mammals. The relatively long humerus and forearm, characteristic for primates, are thus effectively converted into stride length. Observed asymmetries in metric and kinematic behavior of the left and right forelimb are caused by an unequal lateral bending of the spinal column.

Animals↗
PubMed2000

Uniqueness of primate forelimb posture during quadrupedal locomotion.

Among the characteristics that are thought to set primate quadrupedal locomotion apart from that of nonprimate mammals are a more protracted limb posture and larger limb angular excursion. However, kinematic aspects of primate or nonprimate quadrupedal locomotion have been documented in only a handful of species, and more widely for the hind than the forelimb. This study presents data on arm (humerus) and forelimb posture during walking for 102 species of mammals, including 53 nonhuman primates and 49 nonprimate mammals. The results demonstrate that primates uniformly display a more protracted arm and forelimb at hand touchdown of a step than nearly all other mammals. Although primates tend to end a step with a less retracted humerus, their total humeral or forelimb angular excursion exceeds that of other mammals. It is suggested that these features are components of functional adaptations to locomotion in an arboreal habitat, using clawless, grasping extremities.

Adaptation, Physiological↗
PubMed1990

Age- and sex-associated variations in the directional asymmetry of rhesus macaque forelimb bones.

Several investigators have questioned the significance of handedness as an explanation of directional forelimb asymmetries, yet little has been done to isolate other explanatory factors. In this investigation, we analyze 61 female and 76 male rhesus macaque skeletons for evidence of age- and/or sex-associated variations in ten forelimb bone measurements. All significant directional asymmetries are found to favor the right side. Although some of these asymmetries are found to favor the right side. Although some of these asymmetries are compatible with the interpretation of muscle hypertrophy associated with preferential use of the right forelimb, the overall pattern suggests that age- and sex-related ontogenetic factors deserve equal consideration. Significant sex differences in asymmetry means are present within and across age groups (juveniles, subadults, and adults), and numerous changes in asymmetry with age are also found. A pattern of decreasing asymmetry with age was found in males, with 40% of the ten measures being asymmetrical in juveniles, 30% in subadults, and 20% in adults. Among females, this pattern is reversed. No significant asymmetries were found for juvenile or subadult females, whereas 40% of the measures were asymmetrical in adult females. We conclude that greater consideration of age- and sex-related factors is necessary when drawing samples for the purpose of investigating asymmetries, and an awareness of trait-specific age and sex patterns of variation is necessary when citing forelimb asymmetries in demographically nonrepresentative populations as evidence of handedness or other behavioral asymmetries.

Aging↗
PubMed2006

Interactive effects of cadmium and all-trans-retinoic acid on the induction of forelimb ectrodactyly in C57BL/6 mice.

BACKGROUND: Most toxicological studies have tested single chemical agents at relatively high doses, and fewer studies have addressed the toxic effects of chemical interactions. It is important to understand the toxicity of chemical mixtures in order to assess the more realistic risks of environmental and occupational exposures. A number of chemicals are known to induce a predominantly postaxial forelimb ectrodactyly in C57BL/6 mice, including acetazolamide, ethanol, cadmium, valproic acid, carbon dioxide, dimethadione, phenytoin, and 13-cis-retinoic acid and all-trans-retinoic acid (RA). In the present study, the interactive effects of coadministration of cadmium and RA on developing limbs were investigated. METHODS: Pregnant C57BL/6 mice were treated with different intraperitoneal (IP) doses of cadmium chloride (CdCl2) and/or RA on gestational day (GD) 9.5, and fetuses were collected on GD 18 and double stained for examination of skeletal defects. RESULTS: When RA was given simultaneously with cadmium, a significant increase in the incidence and severity of forelimb ectrodactyly (predominantly postaxial) was observed compared to the results with corresponding doses of cadmium or RA alone. When mice were exposed to subthreshold doses of both cadmium (0.5 mg/kg) and RA (1 mg/kg), the combined treatment exceeded the threshold, resulting in forelimb ectrodactyly in 19% of the fetuses. Moreover, coadministration of cadmium and RA at doses exceeding the respective thresholds showed a synergistic effect, that is, 92% of fetuses were found with the forelimb defect as opposed to 10% if the response were additive. CONCLUSIONS: The findings demonstrate that concurrent exposure to these teratogens can have a synergistic effect and that subteratogenic doses may combine to exceed a threshold.

Animals↗
PubMed1981

Anatomical demonstration of multiple representation in the forelimb region of the cat motor cortex.

Retrograde transport of HRP was employed to examine the pattern of callosal connections in the forelimb region of area 4 gamma in the cat. According to the conventional view, areas of the motor cortex which contain the representation of distal body parts neither send nor receive callosal fibers. If this is true, then an absence of callosal connections would define the sites of distal forelimb representation. Following multiple injections of HRP into the contralateral motor cortex, many labeled neurons were found in the forelimb region of area 4 gamma. However, within this region, two spatially separate areas were found where labeled neurons were either absent or present in very low density ("callosal holes"). The anatomically defined callosal holes corresponded in size, shape, and location to the physiologically defined digit zones. To provide direct evidence for this correspondence, retrograde HRP transport was combined with intracortical stimulation in the same animal. Small lesions placed in physiologically identified digit zones were located within the anatomically defined callosal holes. Thus, a double representation of the distal forelimb can be defined in area 4 gamma of the cat motor cortex using both anatomical and physiological methods.

Animals↗
PubMed2001

Differential response of Shh expression between chick forelimb and hindlimb buds by FGF-4.

The interactions of Sonic hedgehog (Shh) and fibroblast growth factor (FGF) play important roles in vertebrate limb pattern formation. In the posterior region of the chick limb bud, Shh and FGF-4 each maintain expression in a positive feedback loop. In the anterior region, Shh can also induce Fgf-4 expression in the anterior apical ectodermal ridge. However, the possibility of Shh induction by FGF protein is unclear. Because many experiments to analyze gene expression have been carried out by using the forelimb bud of the chick embryo, we investigated gene expression of the cells in the anterior region of the chick hindlimb bud after FGF-4 application and compared the results with those for the forelimb bud. When an FGF-4-containing bead was implanted into the anterior region of a stage 20 hindlimb bud, ectopic expression of Shh was induced in the mesenchyme beneath the anterior end of the apical ectodermal ridge at 36 hr after implantation. Subsequent to Shh activation, Hoxd13 was also observed in the anterior-distal region of the limb bud. Furthermore, FGF-4 implantation to the hindlimb bud caused additional digit formation accompanying respecification of positional value in the anterior tissue. Ectopic Shh was induced in cells located distal to the FGF-4 bead, and the cells of the flank region did not contribute to ectopic Shh induction. On the other hand, no ectopic Shh and Hoxd13 expression was detected by grafting an FGF-4 bead into the forelimb bud. Although FGF-4 implantation to the forelimb bud occasionally induced extra digit 2 formation, no embryos had an extra digit 3 or digit 4, and many specimens exhibited normal skeletal pattern. These results demonstrate the difference between the fore- and hindlimb buds in the cell competence of Shh induction in response to FGF-4, suggesting the possibility that the responsiveness of mesenchymal cells in signaling molecules is not the same in the fore- and hindlimb buds.

Animals↗
PubMed1986

Forelimb regeneration in the postmetamorphic bullfrog: stimulation by dimethyl sulfoxide and retinoic acid.

To examine the effects of retinoic acid and dimethyl sulfoxide on regenerative ability of anuran amphibians, the left forelimbs of 60 postmetamorphic froglets of Rana catesbeiana (bullfrogs) were amputated through the distal zeugopodium. Fifteen of the froglets had their left forelimb stumps immersed in dimethyl sulfoxide (DMSO) for 3 minutes, once immediately after amputation and once on each of 5 subsequent days. Another 15 frogs had their left forelimb stumps immersed in a 0.01 M solution of retinoic acid dissolved in DMSO for the same period of time. The remaining 30 control froglets did not regenerate structures distal to the amputation surface, while all limbs in both treated groups produced regenerates by 120 days postamputation. Regenerates of limbs treated with both DMSO alone and DMSO combined with retinoic acid, although hypomorphic, were composed of multiple cartilage elements, which in many cases (46.7%) were organized as patterns partially resembling the skeletal arrangement of a normal forelimb. All of these regenerates exhibited bundles of striated muscle. In addition, nearly half (46.7%) of the regenerates in the DMSO + retinoic acid group possessed two separate regenerate outgrowths. The results demonstrate that young bullfrogs (Rana catesbeiana) possess a latent epimorphic regenerative capability, which can be stimulated by topical application to the wound surface of DMSO alone or DMSO combined with retinoic acid.

Animals↗
PubMed1989

Cellular contribution to symmetrical forelimbs from triploid-marked "polarizing region" in the embryo of axolotl, Ambystoma mexicanum.

Grafts of posterior tissue placed anterior to the limb bud in the salamander embryo exert a polarizing influence. To explain this result, the idea that the anteroposterior axis of the developing forelimb is polarized by a diffusible morphogen has been proposed. An alternative hypothesis, and the working hypothesis of the present study, is that the polarization of the developing salamander forelimb is accomplished by short-range cellular interactions resulting in intercalation rather than by the more global influence of a diffusible morphogen. One prediction of this intercalation hypothesis is that cells will be contributed to the limb from the "polarizing tissue." To test this idea, grafts of triploid marked polarizing tissue were implanted anterior to the limb bud in 82 diploid axolotl embryos at stages 32-34 of development. A total of 27 (33%) of the limbs that resulted were symmetrical and ranged in complexity from one to seven digits. Histological analysis of a subgroup of the original symmetrical limbs revealed that mesodermally derived tissues in the anterior side of these limbs (the side which formed as a duplication in response to the influence of the graft) contained high percentages of trinucleolate cells (muscle, 12.1%; connective tissue tissue, 12.5%; and cartilage, 13.4%) when compared to similar tissues in the posterior side of the same symmetrical limbs (muscle, 1.8%; connective tissue , 0.7%; and cartilage, 0.6%). When symmetrical limbs were amputated, 73% regenerated symmetrical limbs. When these regenerated limbs were again amputated, 63% formed symmetrical secondary regenerates. Histological analysis of the first generation of regenerated limbs revealed that the pattern of distribution of trinucleolate cells in each regenerate was similar to the pattern seen in the original symmetrical limb. These results indicate that there is considerable cellular contribution to the anterior side of the symmetrical forelimb from the mesoderm of grafted "polarizing tissue." This result supports the idea that short-range cellular interaction are sufficient for formation of symmetrical forelimbs in salamander embryos.

Ambystoma↗
PubMed1989

Delayed carpal ossification in Notophthalmus viridescens Efts: Relation to the progress of mesopodial completion in newt forelimb regenerates.

The persistence of cartilage in the adult newt (Notophthalmus viridescens) forelimb skeletal regenerate has recently been reported by Libbon et al. It is particularly evident in the carpal group, which remains cartilaginous for at least 9 months while all other regrown skeletal parts are either ossified or ossifying. The present investigation was undertaken to determine whether delayed ossification in the adult regenerate recapitulates a pattern evident during the development of the forelimb of the red eft (N. viridenscens' immature terrestrial phase). Right upper limbs of 20 efts were examined at low magnification to establish carpal composition and organization. Among five efts of the smallest size (26.54 plus or minus 2.20 mm snout-to-vent length), and displaying bright orange dorsal skin coloration, all carpal rudiments were cartilaginous. Eleven efts, intermediate in length (33.88 plus or minus 0.81 mm), displaying orange-green coloration, all carpals had ossified. These observations demonstrate that during adult newt forelimb regeneration, the failure of the carpal elements to begin ossification in synchrony with other regrown skeletal parts duplicates a similar schedule of delayed mesopodial ossification which is evident during the development of the red eft's forelimb.

Animals↗
PubMed1977

Structural correlates of forelimb function in fur seals and sea lions.

Dissections, manipulation of ligamentary preparations, analysis of limb proportions, and quantitative aspects of forelimb myology are used to correlate forelimb morphology in fur seals and sea lions (sub-family Otariinae) with previously published data as to their locomotor function (English, '76a). Comparisons to structure and function in generalized fissiped carnivores are then used to elucidate locomotor adaptations in fur seals and sea lions. Unique features of forelimb function during swimming in these pinnipeds include the amounts of abduction-adduction and rotary movements used. Modifications of the size, attachments and fasicle architecture of the muscles and the structure and range of possible movement of the joints suggest that in fur seals and sea lions these movements (1) take place about the glenohumeral (shoulder) joints, (2) that the movements are probably finely controlled, and (3) that they contribute to the generation of massive forward thrust via the cooperative activity of muscles capable of generating large amounts of force throughout the range of movement. Recovery movements occur through a similarly large range, and modifications of forelimb anatomy either to minimize or overcome water resistance are noted. The adaptive significance of these modifications is interpreted as allowing fur seals and sea lions to swim at speeds necessary to feed on the fast swimming prey presumably abundant in their adaptive zone.

Animals↗
PubMed2004

Unilateral ischemic sensorimotor cortical damage induces contralesional synaptogenesis and enhances skilled reaching with the ipsilateral forelimb in adult male rats.

Unilateral damage to the forelimb representation area of the sensorimotor cortex (SMC) results in a compensatory reliance on the unimpaired (ipsilateral to the lesion) forelimb as well as reorganization of neuronal structure and connectivity in the contralateral motor cortex. Recently, male rats with unilateral electrolytic SMC lesions were found to have enhanced skilled reaching performance with the ipsilesional forelimb compared with sham-operated controls. The present study was performed to determine whether these behavioral findings are replicable using an ischemic lesion and whether there is a link between the enhanced learning and synaptogenesis in motor cortical layer V opposite the trained limb and lesion, as assessed using stereological methods for light and electron microscopy. Rats were given a sham operation or an endothelin-1 (ET-1) induced ischemic SMC lesion. They were then trained for 20 days on a skilled reaching task with the unimpaired limb or received control procedures. As with previous findings using electrolytic lesions, rats with unilateral ischemic SMC lesions performed significantly better using the unimpaired forelimb than did sham-operates. Lesions, but not training, significantly increased the total number of motor cortical layer V synapses per neuron as well as the number of perforated and multisynaptic bouton (MSB) synapses per neuron compared with shams. Thus, in addition to a net increase in synapses, the improved reaching ability was coupled with an increase in synapse subtypes that have previously been linked to enhanced synaptic efficacy. The failure to induce synaptogenesis in layer V with reach training alone is in contrast to previous findings and may be related to training intensity.

Age Factors↗
PubMed1985

Pathogenesis of the mouse forelimb deformity induced by acetazolamide: an electron microscopic study.

Scanning electron microscopic observations after removal of the epidermis from developing limb buds reveal a fine mesenchymal cell process meshwork (CPM). The relationship between apical ectodermal ridge (AER) development and CPM density was investigated and related to the postaxial reduction deformities induced by acetazolamide (AA). AA was given orally to pregnant mice at 9 A.M. and 4 P.M. of day 9 and 9 A.M. of day 10 (VP = 0) in a dose of 1,000 mg/kg. Forelimb ectrodactyly, especially on the right, was the most common deformity observed. Scanning electron microscopic observations showed that the AER in AA-treated right forelimb buds did not extend postaxially as far as that in controls. The postaxial region with the hypoplastic AER became defective. Scanning and transmission electron microscopic observations revealed that in control and treated right forelimb buds, the CPM underneath the typical AER was sparser than that underneath the dorsal or ventral non-ridge epidermis. However, in treated right forelimb buds, the CPM underneath a hypoplastic AER was denser than that underneath the normal AER. These findings suggest that AA-induced deformity results from a disturbance of the AER-mesenchymal interactions.

Abnormalities, Drug-Induced↗
PubMed2002

The pattern of neurovascular development in the forelimb of the quail embryo.

Peripheral nerve and vascular patterns are congruent in the adult vertebrate, but this has been disputed in vertebrate embryos. The most detailed of these studies have used the avian forelimb as a model system, yet neurovascular anatomical relationships and critical vascular remodeling events remain inadequately characterized in this model. To address this, we have used a combination of intravascular marker injection, multilabel fluorescent stereomicroscopy, and confocal microscopy to analyze the spatiotemporal relationships between peripheral nerves and blood vessels in the forelimb of 818 quail embryos from E2 (HH13) to E15 (HH41). We find that the neurovascular anatomical relationships established during development are highly stereotypic and congruent. Blood vessels typically arise before their corresponding nerves, but there are several critical exceptions to this rule. The vascular pattern is extensively remodeled from the earliest stage examined (E2; HH13), whereas the peripheral nerves, the first of which enter the forelimb at E3.5-E4 (HH21-HH24), have a progressively unfolding pattern that, once formed, remains essentially unchanged. The adult neurovascular pattern is not established until E8 (HH34). Peripheral nerves are always found to track close and parallel to the vasculature. As they track distally, peripheral nerves always lie on the side of the vasculature away from the center of the forelimb. Neurovascular patterns have a hierarchy of congruence that is highest in the dorsoventral plane, followed by the anteroposterior, and lastly the proximodistal planes.

Animals↗