This section is still under
construction.
Genes
Hox
Control of morphogenesis and differentiation
by HOM/Hox genes. Botas, J. Curr. Opin. Cell Biol. 5 1015-1022
(1993).
- These ancient genes have conserved their
function throughout evolution in diverse species. Homeotic
selector genes (HOM) in drosophila and nematodes and Hox genes in
vertebrates.
- This family of genes appear to regulate
axial cell fate in the embryo.
- The genes share structure organization
and expression.
- The homeobox sequence is 180 bp with a
helix-turn-helix motif.
- These proteins are transcription factors
which bind to specific DNA sequences and activate genes.
Murine Development Control Genes, Kessel, M. and Gruss, P. Science
249 374-379 (1990).
- An early review of the genes, and method of identifying them,
involved in early mouse development. In particular discusses
Homeobox genes. (homeobox is 183bp encoding a 61 amino acid
DNA-binding domain)
- Gene families
Early
Development
Establishment of the axis in chordates: facts and speculations, H.
Eyal-Giladl, Development 124:2285-2296 (1997)
Somites
Early stages of chick somite development. Christ, B. and Ordahl,
C.P. Anat. Embryol. 191 381-396 (1995).
Heart
(review)
Fashioning the vertebrate heart: earliest embryonic decisions.
M.C. Fishman and M.C. Chien, Development 124:2099-2117 (1997)
(Mouse)
The allocation of epiblast cells to the embryonic heart and other
mesodermal lineages: the role of ingression and tissue movement
during gastrulation. Tam, P.P.L. et al., Development 124
1631-1642 (1997).
- Epiblast cells aquire a cardiogenic fate without ingression
through the primitive streak or movement within the mesoderm.
Allocation of epiblast cells to a mesodermal lineage appears
dependent upon the timing of recruitment to the primitive streak.
Limbs
Why thumbs are up. Martin, G.R. Nature
374
410-411 (1995).
- Reviews a paper in this issue of Nature
concerning Wnt-7a expression in the limb, but also summarizes the
other polarizing signals in the limb.
Nervous
System
CNS
Determination events in the nervous system of the vertebrate
embryo. Superieure, L.B. and Wassef, M. Curr Opin in Genetics and
Development 5 450-458 (1995).
Evidence for multi-site closure of the neural tube in humans. Van
Allen, M. I. et al., American J of Medical Genetics 47 723-43
(1993).
- Multisite neural tube (NT) closure has been demonstrated in
chicken and mouse embryos.
- This study looks at neural tube defects (NTDs) in humans and
the role of multisite closure.
- Genetic variations of NT closures sites occur in mice and are
evident in humans, e.g., familial NTDs with Sikh heritage (closure
4 and rostral 1), Meckel-Gruber syndrome (closure 4), and
Walker-Warburg syndrome (2-4 neuropore, closure 4).
- Environmental and teratogenic exposures frequently affect
specific closure sites, e.g., folate deficiency (closures 2, 4,
and caudal 1) and valproic acid (closure 5 and canalization).
ABNORMALITIES
Disorders of the central nervous system. Paidas, M. J. and Cohen,
A. Seminars in Perinatology 18 266-282 (1994).
- Review article of most commonly seen CNS abnormalities.
- Dandy-Walker Syndrome, Fetal Diseases, Holoprosencephaly,
Hydrocephalus, Neural Tube Defects, Spina bifida.
Vulnerable periods and processes during central nervous system
development. Rodier, P. M. Environmental Health Perspectives 102
Suppl 2 121-4 (1994).
- The developing CNS lacks a blood brain barrier.
- Known teratogens indicate that differential doses to the
developing vs mature brain are not the major factor in
differential sensitivity.
- Most agents seem to act on processes that occur only during
development: cell proliferation, migration, and differentiation.
- The most important of these is probably the fact that nervous
system development takes much longer than development of other
organs, making it subject to injury over a longer period.
Linkage of a human brain malformation, familial holoprosencephaly,
to chromosome 7 and evidence for genetic heterogeneity. Muenke, M. et
al., PNAS 91 8102-6 (1994).
- Holoprosencephaly (HPE) is a common malformation of the
developing forebrain and midface characterized by incomplete
penetrance and variable expressivity.
- These results show that a gene for autosomal dominant HPE is
located in a chromosomal region (7q36) known to be involved in
sporadic HPE with visible cytogenetic deletions.
Mutations in the human Sonic Hedgehog gene cause
holoprosencephaly. Roessler, E. et al., Nature Genetics 14
357-60 (1996).
- Holoprosencephaly (HPE) is a common developmental defect of
the forebrain and frequently the midface in humans, with both
genetic and environmental causes.
- HPE has a prevalence of 1:250 during embryogenesis and
1:16,000 newborn infants.
- Involves incomplete development and septation of midline
structures in the central nervous system (CNS) with a broad
spectrum of clinical severity.
- Alobar HPE, the most severe form which is usually incompatible
with postnatal life, involves complete failure of division of the
forebrain into right and left hemispheres and is
characteristically associated with facial anomalies including
cyclopia, a primitive nasal structure (proboscis) and/or midfacial
clefting.
- The molecular basis underlying HPE is not known, although
teratogens, non-random chromosomal anomalies and familial forms
with autosomal dominant and recessive inheritance have been
described.
- HPE3 on chromosome 7q36 is one of at least four different loci
implicated in HPE.
- Identification of human Sonic Hedgehog (SHH) as HPE3-the first
known gene to cause HPE.
-
Neural
Crest
Contribution of early-emigrating midbrain
crest cells to the dental mesenchyme of mandibular molar teeth in rat
embryos. Imai, H. et al., Developmental Biology
176 151-65 (1996).
- rat
- Reciprocal interactions between the
epithelium and mesenchyme in the first pharyngeal arch form
teeth.
- This paper does labelling studies in the
rat to observe that early-emigrating posterior midbrain crest
cells (at the end of the 4-somite stage) predominantly migrated to
the region where tooth buds (mandibular molar) normally
develop.
Spatial distribution of postotic crest cells
defines the head/trunk interface of the vertebrate body:
embryological interpretation of peripheral nerve morphology and
evolution of the vertebrate head. Kuratani, S. Anatomy &
Embryology 195 1-13 (1997).
- chicken
- The migration pathways and spatial
distribution of neural crest cells largely depend on the embryonic
architecture.
- Postotic crest is located at the
intermediate level between the trunk and the head, giving rise to
both the cephalic and trunk crest cells. Its cephalic components
circumpharyngeal crest cells, are distributed only rostral to the
S-shaped interface.
Teratogens
Vulnerable periods and processes during central nervous system
development. Rodier, P. M. Environmental Health Perspectives 102
Suppl 2 121-4 (1994).
- The developing CNS lacks a blood brain barrier.
- Known teratogens indicate that differential doses to the
developing vs mature brain are not the major factor in
differential sensitivity.
- Most agents seem to act on processes that occur only during
development: cell proliferation, migration, and differentiation.
- The most important of these is probably the fact that nervous
system development takes much longer than development of other
organs, making it subject to injury over a longer period.
Retinoids as teratogens. Soprano, D. R. and Soprano, K. J. Annual
Review of Nutrition 15 111-32 (1995).
- Review of Vitamin A as a necessary nutrient in the diet.
- Reviews fetal malformations associated with maternal ingestion
of natural and synthetic retinoids in both experimental animals
and humans.
Review of the role of potential teratogens in the origin of human
nonsyndromic oral clefts. Wyszynski, D. F. and Beaty, T. H.
Teratology 53 309-17 (1996).
- Oral clefts occur approx 1 every 1,000 caucasian newborns.
- This is a review of literature on environmental exposures
potentially associated with non-syndromic oral clefts.
