POU domain factor Brn-3a controls the differentiation and survival of trigeminal neurons by regulating Trk receptor expression

Mice lacking the POU domain-containing transcription factor Brn-3a have sev eral neuronal deficits. In the present paper, we show that Brn-3a plays two distinct roles during development of the trigeminal ganglion. In this gang lion, neurons expressing the neurotrophin receptors, TrkB and TrkC, are bor n between E9.5 and E11.5. In the absence of Brn-3a, very few neurons ever e xpress TrkC, but TrkB-expressing neurons are present at E12.5 in elevated n umbers, suggesting that Brn-3a may be a constituent of a regulatory circuit determining which Trk receptor is expressed by these early-born neurons. M ost neurons expressing the neurotrophin receptor TrkA are generated between E11.5 and E13.5 in this ganglion and their initial generation is not preve nted by absence of Brn-3a. However, after E12.5, absence of Brn-3a results in a progressive loss in neuronal TrkA and TrkB expression, which leads to a massive wave of apoptosis that peaks at E15.5, Despite complete absence o f the Trk receptors at E17.5 and PO, approximately 30% of the normal comple ment of neurons survive to birth in Brn-3a mutants. Approximately 70% of th ese express the GDNF receptor subunit, c-ret; many can be sustained by GDNF , but not by NGF in culture. Thus, the vast majority of surviving neurons a re probably sustained in vivo by trophic factor(s) whose receptors are not regulated by Brn-3a, In conclusion, our data indicate the specific function s of Brn-3a in controlling the survival and differentiation of trigeminal n eurons by regulating expression of each of the three Trk receptors.