Fig. 8. The role of CYP1B1 in RA biochemistry and its potential role in patterning the ventral neural tube and motor neuron differentiation. (A) Oxidative cascade leading to the synthesis and breakdown of RA. CYP1B1 can generate retinal and RA but does not subsequently catabolise RA. The other major components of the pathway are shown. In this model, only the ADHs are thought to be ubiquitously expressed, with the others showing developmentally restricted patterns of expression. (B) Expression domains of Shh, homeodomain and bHLH transcription factors in the ventral spinal cord. Mutual cross-repressive interactions between class I and II proteins establish a motor neuron progenitor domain exclusively in the region of PAX6 and NKX6 that is defined by the expression of OLIG2. Later steps in acquisition of a committed motor neuron phenotype are marked by MNR2 and ISL1. RA is known to play a role in the regulation of this process (reviewed by Jessell, 2000). (C) Following overexpression of Cyp1B1 in the ventral neural tube, the phenotypic effects can be explained by a disruption of the pMN domain via the excess production of RA. (D) RA is known to be involved in many other steps (green arrows) of MN specification/maturation (see references listed). RA produced by CYP1B1 could also contribute to these events.