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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
