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Biomedical subjects

G Morriss-Kay

Publications and source records attributed to G Morriss-Kay.

24 records · Page 2Linked to original sources

Fluidity of the neural epithelium during forebrain formation in rat embryos.

During neurulation in rat embryos, the forebrain grows more rapidly than can be accounted for by intrinsic cell division alone, while the adjacent midbrain/rostral hindbrain maintains a constant cell number despite a high mitotic index (the cell cycle time is 6 h throughout the neural epithelium). We have proposed that neuroepithelial cells flow in a rostral direction within the midbrain/rostral hindbrain region, towards and into the rapidly expanding forebrain. Evidence in support of this hypothesis is provided by cell-labelling studies: labelled neuroepithelial cells were injected into specific sites in the midbrain or rostral hindbrain neuroepithelium of unlabelled embryos; after culture of these embryos for 24 h, the labelled cells were found in positions rostral to the injection sites. In the midbrain/rostral hindbrain region, mitotic spindles were found to be predominantly orientated parallel with the long axis of the embryo; transversely orientated spindles were more frequently observed close to the lateral edges than more medially. Neural crest cells emigrate from the lateral edges during neurulation. These observations suggest that mitotic spindle orientation reflects the direction of cell movement: in the lateral region movement towards the lateral edge would maintain cell number in the transverse plane as neural crest cells emigrate; elsewhere, cells are moving mainly in the longitudinal plane, towards the forebrain. The possible causal relationship between cell movement and mitotic spindle orientation is discussed. Cell flow within the intact neural epithelium is compared with cell flow in the intestinal villus epithelium. Other types of epithelial cell movement observed in the cranial neural epithelium during neurulation include expansion and shrinkage of the epithelial surface associated with change of cell shape and microfilament-mediated curvature. Cell rearrangement involving exchange of neighbours and cell movement towards and into a site of epithelio-mesenchymal conversion are also implicated.

Animals↗

Abnormal neural fold development in mouse trisomy 12 and trisomy 14. II. LM and TEM.

LM and TEM observations of embryonic tissue during the period of cranial neurulation are described in trisomic mouse embryos known to develop exencephaly, and are compared with tissue from normal mouse embryos. The earliest regularly observed differences were visible from the late presomite stage onwards, in the extracellular matrix of the cranial region. These were local defects of the basement membrane of the neural epithelium and enlarged areas of mesenchymal extracellular matrix, with associated abnormalities of mesenchymal cell distribution, cell number and cell contacts, and deficiency of alcian blue staining. Apical neuroepithelial microfilament bundles were observed at later somite-stages in trisomic embryos c.f. = compared with controls, and development of the concave neuroepithelial curvature was correspondingly retarded. Apposition of the neural folds at the forebrain/midbrain junction was never made, even though late neural fold fusion occurred in the hindbrain and ventral forebrain. At later stages (9-20 somites) the neuroepithelial cells showed pyknotic nuclei and dense intracellular inclusions. These are interpreted as secondary effects.

Animals↗

The development and distribution of the cranial neural crest in the rat embryo.

The head region of rat embryos was investigated by scanning electron microscopy after removal of the surface ectoderm with adhesive tape. Observations were made in embryos from 6-somite to 11-somite stages of development, in order to determine: (1) the sequence of emigration of neural crest cells from the different regions of the future brain; (2) the appearance of crest cells before, during, and after their conversion from an epithelial to a mesenchymal form; (3) the migration pathways. Emigration occurs first from the midbrain, and next from the rostral hindbrain; crest cells from these two regions migrate into the first visceral arch. Subsequently cells emigrate from the caudal hindbrain, but not in a rostrocaudal sequence. At the time of crest cell emigration, the neural fold morphology varies from a slightly convex, widely open plate (midbrain) to a closed tube (caudal hindbrain). Thus the timing of emigration is related neither to age (as reflected in rostrocaudal levels) nor to morphology of the neural epithelium.

Animals↗

The role of microfilaments in cranial neurulation in rat embryos: effects of short-term exposure to cytochalasin D.

During the late stages of cranial neurulation in mammalian embryos, the neural epithelium becomes concave. A thick subapical band of microfilament bundles, attached to junctions which are both vertical and horizontal in orientation, can be seen by TEM. Prior to this the neural epithelium is first biconvex and then V-shaped in transverse section, microfilament bundles are absent, and the subapical junctions are only vertical in orientation. In order to determine the role of microfilaments in cranial neurulation, rat embryos were exposed to cytochalasin D (0.15 micrograms ml-1) for 1 h at three stages of development: convex neural fold stage, early concave (prior to midline apposition at the forebrain/midbrain junction: 'preapposition') and later concave ('postapposition'). They were subsequently washed and cultured in addition-free medium for 5, 12, 24 or 36 h, then examined alive and by LM, TEM, or SEM. The degree of neural fold collapse varied with the stage of development: at the convex stage there was only slight opening out of the neural groove; early concave (preapposition) neural folds collapsed laterally to a horizontal position; later concave (postapposition) neural folds showed widening of the midbrain/hindbrain neuropore and slight neuroepithelial eversion at the anterior neuropore. Neural epithelium which had been concave prior to cytochalasin D treatment changed in structure so that the cells were broader and shorter; most of the subapical junctions were vertical in orientation, and microfilament bundles were represented either as a mass of amorphous material adjacent to the junctions, or as separated and broken filaments. Re-elevation of neural folds in 'recovery' cultures was accompanied by regeneration of apical microfilament bundles and horizontal junctions. Embryos which had been exposed to cytochalasin D at the convex or later concave stage of cranial neural fold development were able to complete cranial neural tube closure; none of the early-concave-stage embryos achieved apposition at the forebrain/midbrain junction, and all had major cranial neural tube defects. The results suggest that contraction of apical microfilament bundles plays an essential role in elevation of the neural folds and in the generation of concave curvature during the later stages of cranial neurulation. During the convex neural fold stage, microfilaments are important in maintaining neuroepithelial apposition in the neural groove, but are not crucial to maintenance of the convex shape. Successful formation and maintenance of the forebrain/midbrain apposition point at the appropriate time is considered to be essential for subsequent brain tube closure.

Actin Cytoskeleton↗

Early events in mammalian craniofacial morphogenesis.

Head-trunk differences are well established in the most primitive vertebrates, and are clear from early developmental stages of all modern forms. The boundary between the two regions is not constant in all vertebrate classes in terms of the number of occipital somites. The occipital region is in some respects a transitional zone, giving rise to trunk-like somitic derivatives in the head. It is also highly specialised, providing a unique population of neural crest cells that are essential for formation of the aorticopulmonary septum (which divides the outflow tract of the heart) in mammals and birds. In the preoccipital hindbrain, rhombomeres represent a segmental structural pattern that is quite distinct from that of the somites, with a segment-specific pattern of gene expression. Expression of some of these genes in mesenchyme close to the primitive streak at earlier stages suggests that this pattern may be established at the time of neural induction. Mammalian embryos have taken cranial specialization further than other classes of vertebrate, particularly in relation to the pattern of development and eventual structural complexity of the forebrain. Mammalian specialisations of craniofacial development are described through references to studies on cranial neurulation, on cranial neural crest cell migration, and on the possible morphogenetic roles of extracellular matrix components.

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