Biomedical subjects

G E Lyons

Publications and source records attributed to G E Lyons.

At least 55 records · Page 3Linked to original sources

PubMed1995

Expression of mef2 genes in the mouse central nervous system suggests a role in neuronal maturation.

Members of the myocyte enhancer factor 2 (MEF2) gene family are expressed in a dynamic pattern during development of the CNS of pre- and postnatal mice. The four MEF2 genes, Mef2A, -B, -C, -D, encode transcription factors belonging to the MADS (MCM1-agamous-deficiens-serum response factor) superfamily of DNA binding proteins. MEF2 factors have previously been shown to be positive regulators of gene expression in terminally differentiated muscle cells. To begin to determine the role of MEF2 factors in CNS development, we used in situ hybridization with gene-specific cRNA probes to define the expression patterns of each of the four Mef2 mRNAs in the developing and mature mouse CNS. Mef2C mRNA was first detected in a ventral portion of the telencephalon at 11.5 d postcoitum (p.c.). By 13.5 d p.c., each of the four Mef2 genes were expressed in overlapping yet distinct patterns in regions of the frontal cortex, midbrain, thalamus, hippocampus, and hindbrain. Temporal and spatial patterns of embryonic Mef2 gene expression appeared to follow gradients of neuron maturation and suggested that the onset of Mef2 gene expression coincides with withdrawal from the cell cycle and initiation of neuronal differentiation. This correlation is particularly striking for Purkinje cells in the cerebellum. Since the molecular mechanisms that regulate neuron differentiation are unknown, we propose that the MEF2 factors are likely to play an important role in this process.

Animals↗

PubMed1994

Bone morphogenetic protein-1 and a mammalian tolloid homologue (mTld) are encoded by alternatively spliced transcripts which are differentially expressed in some tissues.

Bone morphogenetic protein-1 (BMP-1) is a metalloprotease purified from extracts capable of inducing ectopic bone formation. In humans, it has a domain structure similar to that of the Drosophila dorsal-ventral patterning gene-product tolloid (Tld), but is considerably shorter. Here we show that, in humans and mice, alternatively spliced transcripts encode BMP-1 and a longer protein, designated mammalian tolloid (mTld), with a domain structure identical to that of Drosophila Tld. A third alternatively spliced product, in which a novel domain is inserted near the BMP-1 C terminus, is also reported. Low levels of transcripts for mTld were found in all adult human tissues surveyed, while BMP-1 transcripts were detectable in all adult tissues except brain. This differential expression was mirrored in embryonic mouse tissues where in situ hybridization found high levels of mTld transcripts, but was unable to detect BMP-1 transcripts, in the floor plate of the neural tube of the developing central nervous system. The third alternatively spliced form was not detected in adult human tissues. In situ hybridizations found punctate signals for all three forms localized to trophoblast giant cells in 17.5-day mouse placenta, with highest levels of expression, especially for BMP-1, near the maternal interface.

Alternative Splicing↗

PubMed1994

A human POU domain gene, mPOU, is expressed in developing brain and specific adult tissues.

POU domain genes constitute a family of transcription factors that exhibit distinct temporal and spatial patterns of expression. To investigate the possible functions that POU proteins may have in muscle development we have isolated four novel POU-domain-encoding sequences from human muscle tissue. One of these sequences, referred to as mPOU, encodes a new member of subclass VI of the POU family. In the embryo, mPOU is expressed exclusively in the developing brain, whereas in the adult its expression is restricted to brain, heart, skeletal muscle and lung. In the brain, the highest expression levels were found in specific cell layers of the cortex, the olfactory bulb, the hippocampus and the cerebellum. mPOU is shown to bind to DNA sequences containing the octamer motif and other POU factor target sites. The distinct expression pattern and divergent DNA-binding characteristics indicate that mPOU may regulate a distinct set of genes.

Amino Acid Sequence↗

PubMed1994

Protooncogene c-ski is expressed in both proliferating and postmitotic neuronal populations.

The cellular protooncogene, c-ski, is expressed in all cells of the developing mouse at low but detectable levels. In situ hybridization and Northern blot analyses reveal that some cells and tissues express this gene at higher levels at certain stages of embryonic and postnatal development. RT-PCR results indicate that alternative splicing of exon 2, known to occur in chickens (Sutrave and Hughes [1989] Mol. Cell. Biol. 9:4046-4051; Grimes et al. [1993] Oncogene 8:2863-2868) does not occur in adult mouse tissues. In the embryo, neural crest cells express the c-ski gene during migration at 8.5 to 9.5 days post coitum (p.c.). Neural crest derivatives such as dorsal root ganglia and melanocytes stain positively with an antibody to the ski protein. At 9 days p.c., the entire neural tube has high levels of c-ski gene expression. By 12-13.5 days only the ependymal layer expresses c-ski above background levels. At 14-16 days p.c., c-ski mRNAs are detected at high levels in the cortical layers of the brain and in the olfactory bulb. In 2 week and 6 week postnatal brains, c-ski gene transcripts are also detected in the hippocampus and in the granule cell layer of the cerebellum. The allantois and placenta exhibit high levels of c-ski mRNAs. Neonatal lung tissue increases c-ski gene expression approximately two-fold compared to prenatal levels. These results suggest that ski plays a role in both the proliferation and differentiation of specific cell populations of the central and peripheral nervous systems and of other tissues.

Alternative Splicing↗

PubMed1994

Recombinant limbs as a model to study homeobox gene regulation during limb development.

Recombinant limb buds constructed of an ectodermal jacket containing dissociated anterior wing bud mesoderm cells form limb-like structures lacking anteroposterior polarity. Polarity can be restored by implanting a small piece of polarizing region into the recombinant limb. We used recombinant limbs to study expression of Msx1 and Msx2 and 5' Hoxd genes in limb development. Detectable mesodermal expression of Msx1 and Msx2 was lost during preparation of the recombinants. When expression was restored both genes were expressed in a symmetrical fashion in the apical mesoderm whether or not the recombinant was polarized. The normal anterior pattern of Msx1 and Msx2 was never reestablished. The roles Msx1 and Msx2 play in limb patterning are at present not clear. In nonpolarized recombinant limbs the 5' Hoxd genes were sequentially and uniformly expressed in the subridge mesoderm across the anteroposterior axis. They exhibited nested domains of expression showing exclusively distal restriction. In polarized recombinants the 5' Hoxd genes were expressed progressively in an asymmetric, nested fashion adjacent to the implanted polarizing region; there was also a distal mesodermal region further from the implant that did not express the most 5' Hoxd genes. Both of these observations are similar to the normal limb. Our results demonstrate that the polarizing region is not necessary for the activation or maintenance of 5' Hoxd gene expression but that its presence is required in order for the normal pattern to be established. We propose that the expression of the Hoxd genes is an intrinsic property of rapidly growing limb cells and that their expression is related to the limb bud proximodistal outgrowth. Our data also support the influence of the polarizing region upon Hoxd gene expression in two ways. First there is a short-range action responsible for the normal asymmetric expression and second a long-range effect suppressing the expression of 5'-Hoxd genes by the anterior cells.

Animals↗

PubMed1994

Mef2 gene expression marks the cardiac and skeletal muscle lineages during mouse embryogenesis.

Members of the MEF2 family of transcription factors bind a conserved A/T-rich sequence in the control regions of many skeletal and cardiac muscle genes. To begin to assess the roles of the different Mef2 genes in the control of muscle gene expression in vivo, we analyzed by in situ hybridization the expression patterns of the Mef2a, Mef2c and Mef2d genes during mouse embryogenesis. We first detected MEF2C expression at day 7.5 postcoitum (p.c.) in cells of the cardiac mesoderm that give rise to the primitive heart tube, making MEF2C one of the earliest markers for the cardiac muscle lineage yet described. By day 8.5, MEF2A, MEF2C and MEF2D mRNAs are all detected in the myocardium. By day 9.0, MEF2C is expressed in rostral myotomes, where its expression lags by about a day behind that of myf5 and several hours behind that of myogenin. MEF2A and MEF2D are expressed at a lower level than MEF2C in the myotome at day 9.5 and are detected in more embryonic tissues than MEF2C. Expression of each of the MEF2 transcripts is observed in muscle-forming regions within the limbs at day 11.5 p.c. and within muscle fibers throughout the embryo at later developmental stages. The expression of MEF2C in the somites and fetal muscle is distinct from that of MEF2A, MEF2D and the myogenic bHLH regulatory genes, suggesting that it may represent a distinct myogenic cell type. Neural crest cells also express high levels of MEF2 mRNAs between days 8.5 and 10.5 of gestation. After day 12.5 p.c., MEF2 transcripts are detected at high levels in specific regions of the brain and ultimately in a wide range of tissues. The distinct patterns of expression of the different Mef2 genes during mouse embryogenesis suggest that these genes respond to unique developmental cues and support the notion that their products play roles in the regulation of muscle-specific transcription during establishment of the cardiac and skeletal muscle lineages.

Animals↗

PubMed1994

Renin mRNA is synthesized locally in rat ocular tissues.

Components of the Renin Angiotensin System (RAS) have been detected in ocular tissues and fluids. The source of the ocular RAS proteins is unknown but possibilities include diffusion or leakage from the systemic circulation, specific uptake from the blood, or local synthesis. We have used RT-PCR and in situ hybridization (ISH) to show that renin mRNA is present in ocular tissues from 3 strains of rats. By RT-PCR, we found 10 of 15 ciliary body samples, 13 of 16 iris samples, and 1 of 3 retina samples were positive for renin mRNA. Also, 6 of 6 brain and 7 of 8 kidney samples were positive. Using ISH, we found renin mRNA in the ciliary muscle adjacent to the sclera extending into the choroid. Tissue near the outflow channels of the anterior chamber angle also labeled. Retinal labeling was weak but present in the nerve fiber layer. Clusters of grains, possibly representing blood vessels, were also seen in the ciliary body, iris, and retina using ISH. These results suggest the presence of a local ocular RAS.

Animals↗

PubMed1993

Isolated sequences from the linked Myf-5 and MRF4 genes drive distinct patterns of muscle-specific expression in transgenic mice.

In developing mouse embryos, MyoD family regulatory genes are expressed specifically in muscle precursors and mature myofibers. This pattern, taken together with the well-established ability of MyoD family members to convert a variety of cell types to skeletal muscle, suggests a significant role for these genes in regulating skeletal myogenesis. The possibility that expression of these genes may be causally associated with segregation of the myogenic lineage from other mesodermal derivatives, or with the subsequent maintenance of muscle phenotypes at later times, raises the issue of how MyoD family genes are themselves regulated during development. In this work, we have initiated studies to identify DNA sequences that govern Myf-5 and MRF4 (herculin, myf-6) transcription. Myf-5 is the first of the MyoD family to be expressed in the developing mouse embryo, while MRF4 is the most abundantly expressed myogenic factor in postnatal animals. In spite of their strikingly divergent patterns of expression, Myf-5 and MRF4 are tightly linked in the mouse genome; their translational start codons are only 8.5 kilobases apart. Here, the 5' flanking regions of the mouse Myf-5 and MRF4 genes were separately linked to a bacterial beta-galactosidase (lacZ) gene, and these constructs were each used to produce several lines of transgenic mice. Transgene expression was monitored by X-gal staining of whole embryos and by in situ hybridization of embryo sections. For the Myf-5/lacZ lines, the most intense transgene expression was in the visceral arches and their craniofacial muscle derivatives, beginning at day 8.75 post coitum (p.c.). This correlates with endogenous Myf-5 expression in visceral arches.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Myogenesis in the mouse.

The first striated muscle to form during mouse embryogenesis is the heart followed by skeletal muscle which is derived from the somites. The expression of genes encoding muscle structural proteins and myogenic regulatory sequences of the MyoD1 family has been examined using 35S-labelled riboprobes. In the cardiac tube, actin and myosin genes are expressed together from an early stage, whereas in the myotome, the earliest skeletal muscle, they are activated asynchronously over days. They are not expressed in the somite prior to myotome formation. One potential muscle marker, carbonic anhydrase III, is expressed in early mesoderm and subsequently in the notochord, similarly to the Brachyury gene. The myogenic sequences are not detectable in the heart. In the myotome they show distinct patterns of expression; this is discussed in the context of their role as muscle transcription factors. myf-5 is the only myogenic factor sequence present in the somite prior to muscle formation and thus is potentially involved in an earlier step of muscle determination. It is also present in the early limb bud, but the status of myogenic precursor cells in the limb in this context is less clear.

Actins↗

PubMed1992

Expression of NCAM isoforms during skeletal myogenesis in the mouse embryo.

We have examined the developmental patterns of neural cell adhesion molecule (NCAM) gene expression in embryonic mouse skeletal muscle cells by in situ hybridization. Moreover, by utilising exon-specific cRNA probes, we have examined tissue specific splicing of the NCAM gene. We show that there is a distinct sequence of NCAM isoform expression during skeletal muscle development. Since NCAMs are also expressed in other cell types, particularly neurons, NCAM mRNAs have been colocalised with acetylcholine receptor alpha (AChR alpha) gene transcripts to identify muscle-specific expression. NCAM is first detected in somites as they first form, prior to their differentiation into muscle and nonmuscle compartments. Myotomes, the first skeletal muscle masses to form in the embryo, express mRNAs for the transmembrane 180 and 140 kDa isoforms of NCAM. Both of these transcripts are also detected in the neural tube, and their spatial pattern of expression changes with development. Transcripts containing the muscle-specific domain (MSD) of the NCAM gene are not detected prior to 11 days postcoitum (p.c.), at a time when rostral somites already contain well-developed myotomes. As the level of MSD mRNAs increases at 12 days p.c., the 140 and 180 kDa transcript levels decrease in skeletal muscle masses. The level of all NCAM isoform transcripts declines between 13 and 15 days p.c. in muscle. However, the 180 and 140 kDa NCAM isoforms are expressed at a high level in neural tissue and in other locations in the developing embryo such as in smooth muscle, around vibrissae follicles, and in the perichondrial zone of digits.

Animals↗

PubMed1992

Multiple sites of Hox-7 expression during mouse embryogenesis: comparison with retinoic acid receptor mRNA localization.

We report results from a study of Hox-7 expression during mouse embryonic and fetal development and compare the localization of Hox-7 transcripts with those of the retinoic acid receptors. Transcripts were detected by in situ hybridization. Hox-7 expression occurs in (1) cephalic neural crest and its derivatives, (2) sites of ectomesodermal interaction, (3) extraembryonic tissues, and (4) endocardial cells. Hox-7 does not seem to be involved in defining rostrocaudal boundaries, but instead appears to be expressed along the proximodistal axes at these sites. We further investigated the active sites of morphogenesis, which involve an ectomesodermal interaction (e.g., limb buds, visceral arches), including genital tubercle and tail ridge. These are regions highly positive for Hox-7 transcripts, and many are known to be sites for the expression of gamma-retinoic acid receptors (RARs) and cellular retinoic acid binding proteins. Most regions that express Hox-7 are subregions of gamma-RAR expression. In the developing limb bud, expression of Hox-7 takes place in the interdigital region, where it overlaps areas of beta-RAR expression.

Animals↗

PubMed1992

Localization of dystrophin gene transcripts during mouse embryogenesis.

The spatial and temporal expression of the dystrophin gene has been examined during mouse embryogenesis, using in situ hybridization on tissue sections with a probe from the 5' end of the dystrophin coding sequence. In striated muscle, dystrophin transcripts are detectable from about 9 d in the heart and slightly later in skeletal muscle. However, there is an important difference between the two types of muscle: the heart is already functional as a contractile organ before the appearance of dystrophin transcripts, whereas this is not the case in skeletal muscle, where dystrophin and myosin heavy chain transcripts are first detectable at the same time. In the heart, dystrophin transcripts accumulate initially in the outflow tract and, at later stages, in both the atria and ventricles. In skeletal muscle, the gene is expressed in all myocytes irrespective of fiber type. In smooth muscle dystrophin transcripts are first detectable from 11 d post coitum in blood vessels, and subsequently in lung bronchi and in the digestive tract. The other major tissue where the dystrophin gene is expressed is the brain, where transcripts are clearly detectable in the cerebellum from 13 d. High-level expression of the gene is also seen in particular regions of the forebrain involved in the regulation of circadian rhythms, the endocrine system, and olfactory function, not previously identified in this context. The findings are discussed in the context of the pathology of Duchenne muscular dystrophy.

Animals↗

PubMed1991

The muscle regulatory gene, Myf-6, has a biphasic pattern of expression during early mouse development.

The spatial and temporal expression pattern of the muscle regulatory gene Myf-6 (MRF4/herculin) has been investigated by in situ hybridization during embryonic and fetal mouse development. Here, we report that the Myf-6 gene shows a biphasic pattern of expression. Myf-6 transcripts are first detected in the most rostral somites of the mouse embryo at 9 d of gestation and accumulate progressively in myotomal cells along the rostro-caudal axis. This expression is transient and Myf-6 mRNA can no longer be detected in myotomal cells after day 12 post coitum (p.c.). In contrast to other muscle determination genes (MyoD1, myogenin, Myf-5), Myf-6 mRNA is not detected in limb buds or visceral arches and skeletal muscle of the mouse embryo (day 8-15 p.c.). In fetal mice, Myf-6 transcripts appear at day 16 p.c. in all skeletal muscles, and the gene continues to be expressed at a high level after birth. These results suggest that early Myf-6 expression may be restricted to a population of myogenic cells that does not contribute to the embryonic muscle masses in limb buds and visceral arches. The reappearance of Myf-6 mRNA in fetal skeletal muscle coincides approximately with secondary muscle fiber formation and the onset of innervation.

Base Sequence↗

PubMed1991

Carbonic anhydrase III, an early mesodermal marker, is expressed in embryonic mouse skeletal muscle and notochord.

Carbonic anhydrase III (CAIII) is an abundant soluble protein in adult mammalian slow twitch skeletal muscle fibers. It is thought to be an early marker for myogenesis based upon its high level of expression in myoblasts in vitro prior to fusion. Using in situ hybridization, we have studied the in vivo distribution of CAIII gene transcripts in mouse embryos and fetuses from 7.25 days to 17.5 days post coitum (p.c.). CAIII mRNAs are first detected in the myotomes of somites between 9.5 and 10.5 days p.c. (20-30 somites). At 15.5 days p.c., CAIII begins to be restricted to developing slow muscle fibers. By two weeks post partum (p.p.), CAIII mRNAs are detected mainly in slow muscle fibers. CAIII transcripts are detected at an earlier stage (7.25 days p.c.) in the developing notochord. CAIII is expressed at a much higher level in the notochord than it is in developing skeletal muscle. As the notochord forms the nucleus pulposus in fetal mice, CAIII mRNA levels remain very high. Expression of CAIII in the notochord is of interest in the context of skeletal myogenesis because the notochord is thought to play an important role in somite formation. In addition to the notochord, CAIII transcripts are detected prenatally in several other non-muscle tissues: in cells of the choroid plexus, endocardial cushion and ureter, and in adipocytes.

Adipose Tissue, Brown↗

PubMed1991

alpha-Actin proteins and gene transcripts are colocalized in embryonic mouse muscle.

The alpha-actins are among the earliest muscle-specific mRNAs to appear in developing cardiac and skeletal muscle. To determine if there is coexpression of the alpha-actin proteins at early stages of myogenesis, we have used an alpha-actin-specific polyclonal antibody and in situ hybridization with specific cRNA probes to cardiac and skeletal alpha-actin transcripts on serial slides of mouse embryo sections. As soon as we can detect alpha-actin mRNAs in embryonic striated muscle, we also detect the protein suggesting that alpha-actin transcripts are translated very rapidly after transcription during myogenesis. In skeletal muscle, this colocalization of alpha-actin mRNA and protein was observed both in the myotomes of somites and in developing muscles in the limbs. In cardiac muscle, alpha-actin transcripts and proteins are abundantly expressed as soon as a cardiac tube forms.

Actins↗

PubMed1991

Developmental regulation of creatine kinase gene expression by myogenic factors in embryonic mouse and chick skeletal muscle.

The B isoform of creatine kinase (BCK), which is expressed at a high level in embryonic neural tissues, is also expressed abundantly in developing striated muscle and is an early marker for skeletal myogenesis. Using isoform-specific 35S-labeled antisense cRNA probes for in situ hybridization, we have detected BCK mRNAs in embryonic mouse and chick myotomes, the first skeletal muscle masses to form in developing embryos. These transcripts are detectable as soon as myotomes are morphologically distinguishable. BCK is expressed at high levels in both skeletal and cardiac muscle in mouse and chick embryos. In the mouse, BCK transcript levels fall of rapidly in striated muscle shortly after the onset of MCK gene expression. The M isoform of creatine kinase (MCK), the striated muscle-specific isoform, is expressed later than BCK. In the mouse, BCK transcripts are expressed in myotomes at 8.5 days post coitum (p.c.), but MCK transcripts are not detected before 13 days p.c. In the chick, BCK mRNAs are present at Hamburger-Hamilton stage 13, but MCK mRNAs are not detected before stage 19. We have compared the patterns of expression of the CK genes with those of myogenic differentiation factor genes, which are thought to regulate skeletal muscle-specific gene expression. In the chick, both CMD1, first detected at stage 13, and myogenin, first detected at stage 15, are present prior to MCK, which begins to be expressed at stage 19. Unlike the mouse embryo, CMD1, the chick homologue of MyoD1, is expressed before chick myogenin. In the mouse, myogenin, first detected at 8.5 days p.c., is expressed at the same time as BCK in myotomes. Both myogenin and MyoD1, which begins to be detected two days later than myogenin, are expressed at least two days before MCK. It has been proposed that the myogenic factors, MyoD1 and myogenin, directly regulate MCK gene expression in the mouse by binding to its enhancer. However, our results show that MCK transcripts are not detected until well after MyoD1 and myogenin mRNAs are expressed, suggesting that these factors by themselves are not sufficient to initiate MCK gene expression.

Animals↗

PubMed1990

The expression of myosin genes in developing skeletal muscle in the mouse embryo.

Using in situ hybridization, we have investigated the temporal sequence of myosin gene expression in the developing skeletal muscle masses of mouse embryos. The probes used were isoform-specific, 35S-labeled antisense cRNAs to the known sarcomeric myosin heavy chain and myosin alkali light chain gene transcripts. Results showed that both cardiac and skeletal myosin heavy chain and myosin light chain mRNAs were first detected between 9 and 10 d post coitum (p.c.) in the myotomes of the most rostral somites. Myosin transcripts appeared in more caudal somites at later stages in a developmental gradient. The earliest myosin heavy chain transcripts detected code for the embryonic skeletal (MHCemb) and beta-cardiac (MHC beta) isoforms. Perinatal myosin heavy chain (MHCpn) transcripts begin to accumulate at 10.5 d p.c., which is much earlier than previously reported. At this stage, MHCemb is the major MHC transcript. By 12.5 d p.c., MHCpn and MHCemb mRNAs are present to an equal extent, and by 15.5 d p.c. the MHCpn transcript is the major MHC mRNA detected. Cardiac MHC beta transcripts are always present as a minor component. In contrast, the cardiac MLC1A mRNA is initially more abundant than that encoding the skeletal MLC1F isoform. By 12.5 d p.c. the two MLC mRNAs are present at similar levels, and by 15.5 d p.c., MLC1F is the predominant MLC transcript detected. Transcripts for the ventricular/slow (MLC1V) and another fast skeletal myosin light chain (MLC3F) are not detected in skeletal muscle before 15 d p.c., which marks the beginning of the fetal stage of muscle development. This is the first stage at which we can detect differences in expression of myosin genes between developing muscle fibers. We conclude that, during the development of the myotome and body wall muscles, different myosin genes follow independent patterns of activation and accumulation. The data presented are the first detailed study of myosin gene expression at these early stages of skeletal muscle development.

Animals↗

PubMed1990

Developmental regulation of myosin gene expression in mouse cardiac muscle.

Expression of the two isoforms of cardiac myosin heavy chain (MHC), MHC alpha and MHC beta, in mammals is regulated postnatally by a variety of stimuli, including serum hormone levels. Less is known about the factors that regulate myosin gene expression in rapidly growing cardiac muscle in embryos. Using isoform-specific 35S-labeled cRNA probes corresponding to the two MHC genes and the two myosin alkali light chain (MLC) genes expressed in cardiac muscle, we have investigated the temporal and spatial pattern of expression of these different genes in the developing mouse heart by in situ hybridization. Between 7.5 and 8 d post coitum (p.c.), the newly formed cardiac tube begins to express MHC alpha, MHC beta, MLC1 atrial (MLC1A), and MLC1 ventricular (MLC1V) gene transcripts at high levels throughout the myocardium. As a distinct ventricular chamber forms between 8 and 9 d p.c., MHC beta mRNAs begin to be restricted to ventricular myocytes. This process is complete by 10.5 d p.c. During this time, MHC alpha mRNA levels decrease in ventricular muscle cells but continue to be expressed at high levels in atrial muscle cells. MHC alpha transcripts continue to decrease in ventricular myocytes until 16 d p.c., when they are detectable at low levels, but then increase, and finally replace MHC beta mRNAs in ventricular muscle by 7 d after birth. Like MHC beta, MLC1V transcripts become restricted to ventricular myocytes, but at a slower rate. MLC1V mRNAs continue to be detected at low levels in atrial cells until 15.5 d p.c. MLC1A mRNA levels gradually decrease but are still detectable in ventricular cells until a few days after birth. This dynamic pattern of changes in the myosin phenotype in the prenatal mouse heart suggests that there are different regulatory mechanisms for cell-specific expression of myosin isoforms during cardiac development.

Aging↗