Threshold dependent BMP Signaling:

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Threshold dependent BMP Signaling: A Conserved Mechanism for Patterning the Ectoderm Ethan Bier Section of Cell and Developmental Biology, UCSD

Epi Neuro Neuro Dorsal Meso snail dpp “sog” sog

Sog blocks BMP invasion of the neuroectoderm Mesodermal Genes Neuronal Genes Epidermal Genes Neuronal Genes BMP B r k Sog Dorsal = M e s o d r m N n - u a l E c t

X Neural Genes are Repressed By BMP Signaling Mesodermal Genes Neuronal Genes Sog Neuronal Genes Epidermal Genes B r k X Dpp = M e s o d r m N n - u a l E c t

Neural Genes are Repressed By BMP Signaling Neuronal Genes Mesodermal Genes = M e s o d r m N n - u a l E c t

Neural Genes are Repressed By BMP Signaling dpp- wt l’sc tkv

X Dpp Invades the Neuroectoderm of sog- Mutants Epidermal Genes Dpp Mesodermal Genes Neuronal Genes Epidermal Genes Neuronal Genes Dpp X Sog = M e s o d r m N n - u a l E c t

Dpp Invades the Neuroectoderm of sog- Mutants Epidermal Genes Neuronal Genes Dpp Mesodermal Genes = M e s o d r m N n - u a l E c t

Dpp Invades the Neuroectoderm of sog- Mutants wt sog-; Dpdpp

The Default state of Ectoderm is Neural

Subdivision of the neuroectoderm Dorsal Dpp Non-neural genes Neural genes Sog B r k

Subdivision of the neuroectoderm Dorsal Dpp Non-neural genes Neural genes Neuronal genes Msh Ind Vnd

Patterning the neuroectoderm in flies and mice Dorsal Dpp ind msh vnd dpp Drosophila Neuroectoderm Mouse Neural Tube Sonic Hh BMPs Msx Nkx2.2 Gsh

Ventral dominance Ventral dominant repression D msh ind vnd V

Generating lateralized embryos ECT 3 2 NE 2 1 MES Mid-lateralized Embryos -> Uniform “ind” levels of Dorsal st2-dpp “ind”

Gene expression in lateralized embryos Mid-Lateralized Embryos ind msh vnd dpp Dorsal

Localized Dpp activity along the A/P axis sog+ sog dpp pMAD sog dpp pMAD sog-

Subdivision of the neuroectoderm dpp merge

Gene expression borders shift in BMP- cells ECT NE MES 1 3 2 st2-brk Brk Dpp st2-brk

Dosage dependent BMP-repression in vertebrates

BMPs can pattern lateralized vertebrate embryos

Conserved Patterning of the Neuroectoderm? Drosophila Neuroectoderm Nkx2.2 Gsh/Pax6 Msx1/2 BMP4 Chd Ventral Midline = Floorplate Vertebrate Neuroectoderm msh vnd ind Dpp Sog Ventral Midline