Download March 9, 2010

March 9, 2010
Drosophila blastoderm fate map
Wild type
poked at front
From bicoid/bicoid mother
hunchback/hunchback embryo
Drosophila embryo
MATERNAL-EFFECT GENES
Gap genes
Pair-rule genes
Segment-polarity genes
Segment-identity, or
homeotic genes
The homeotic mutations identify segment identity genes
Wild type
Bithorax mutant
Atavism is the
recapitulation of
evolutionary ancestral
traits due to mutations
Examples for atavistic traits in humans
Wild type
Antennapedia mutant
Wild type
Proboscipedia mutant
http://www.usask.ca/communications/ocn/may4-01/images/nazaralibugs.jpg
The homeotic genes
The homeotic genes
HOMEOBOX
HOMEODOMAIN
http://www.bmb.psu.edu/faculty/tan/lab/gallery/434reprdna.jpg
The homeotic genes
Construction of knock-out mice from cultured cells
- From embryonic stem cells (ES)
- From embryonic germ-line cells (EG)
- From teratoma or teratocarcinoma cells
From embryonic stem cells (ES)
Embryonic stem cells (ES)
Origin of Stem Cells in the mammalian embryo
Teratoma
Method to generate knock out mutant allele
Electroporation
Homologous
recombination
Embryonic
Embryonic
stem cell stem cell with a mutant
and a normal allele
neoR
neoR
Cultured embryonic
stem cells
Method to generate
knockout mice
Wild type
Mutant
Compare a normal mouse (top) with one that has had Hox10 genes disabled (bottom).
Ribs grow from vertebrae all the way from the chest to the tail
http://www.abc.net.au/science/news/img/life/mouse_skeleton.jpg
Limb bud formation
Apical
Ectodermal
Ridge
Molecular model for the initiation of the limb bud.
A molecular model for the initiation of the limb bud. FGF10 secreted by the lateral plate
mesoderm induces FGF8 expression in the competent ectoderm at the dorsal-ventral boundary.
The anterior-posterior boundary is present at stage 16 (and perhaps earlier). The FGF8 secretion
by the ectoderm induces the proliferation of the mesenchyme cells and induces Sonic hedgehog
expression in the posterior region of the limb bud. Sonic hedgehog induces FGF4 expression in the
posterior portion of the limb bud ectoderm. FGF2 is also made by the AER ectoderm, although it
is not yet clear whether it is induced by the FGF10.
http://www.ncbi.nlm.nih.gov/books/bv.fcgi?highlight=fgf10&rid=dbio.figgrp.3953
Function of the a Tbx5 gene is out function in the Holt-Oram syndrome people
Function of the Hox genes in limb development
http://www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View..ShowSection&rid=dbio.figgrp.3955
Function of Apical Ectodermal Ridge (AER) in limb development
Young limb bud
AER
Old limb bud
Mesoderm
AER
Young limb bud
Old limb bud
Old limb bud
Young limb bud
Contergan babies
Thalidomide
Split hand - split foot syndrome
A consequence of
abnormal AER function
www.thefetus.net/page.php?id=374
The Zone of Polarizing Activity (ZPA) cells secrete Shh
Role of the ZPA cells in anterior/posterior differentiation
The dorsal/ventral differentiation
Determination of dorsal/ventral polarity
Gene expression along the limb bud D/V axis. The member of Wnt family Wnt-7a and
Radical fringe (r-Fng), which encode secreted factors, are expressed in the dorsal ectoderm.
The homeodomain-containing factors encoded by Lmx-1 and Engrailed-1 (En-1) localize to
the dorsal mesoderm and ventral ectoderm, respectively.
http://www.evol.nw.ru/labs/lab38/spirov/gifs/limb-net.gif
The Lmx1 gene does not function in the Nail-patella syndrome people
Possibilities for prenatal diagnosis
- Cells from amnion fluid
- Chorionic villi
- Umbilical vein
- Blood of the mother