Fig. 7. Regulation of BMP activity in rostral neural patterning. (A) Schematic representation of headfold/early somite stage neural plate with surrounding non-neural ectoderm and adjacent axial mesendoderm (after Rubenstein and Beachy, 1998). (B) In wild type, Chrd and Nog (blue crosses) are co-expressed with Fgf8 (yellow) in the anterior neural ridge (ANR). Here, CHRD and NOG antagonize (represented by blunted blue arrow) the activity of BMPs (red arrows) secreted from the non-neural ectoderm abutting the neural plate. This promotes expression of Fgf8, and its function (yellow arrow). Chrd and Nog are also co-expressed with Shh (green) in the caudal prechordal plate (PrCP) and notochord. Here, CHRD and NOG antagonize BMPs expressed in axial mesendoderm and adjacent paraxial mesoderm, permitting SHH signaling from the rostral PrCP (green arrows). (C) In affected Chrd^-/-;Nog^+/- mutants, BMP antagonist expression is reduced in the ANR and the PrCP (fewer blue crosses), and thus, BMP antagonism is reduced (smaller blunted arrows). In turn, expression of Fgf8 is repressed by BMPs in the ANR, reducing its activity (smaller yellow arrow) in adjacent tissues. Similarly, BMPs repress expression of Shh in the rostral PrCP, reducing its activity in surrounding tissues (smaller green arrows). In combination, these defects result in diminished growth and incorrect patterning of the rostral neural plate.

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