Characterization of retinal ganglion cell, horizontal cell, and amacrine cell types expressing the neurotrophic receptor tyrosine kinase Ret
Tightly connected to the characterization of neuronal cell types, is the question of how these neurons develop, differentiate, and acquire their final distinctive features. One key mechanism involves transcription factors (TFs) that regulate the developmental programs of cell fate specification. The transcriptional cascade for RGC specification involves cell fate determination genes, typically active in the still proliferating neuroblasts (Atoh7/Math5) as well as RGC determining factors, such as Isl1 and Pou4f2/Brn3b (Brown, Patel, Brzezinski, & Glaser, 2001; Gan et al., 1996; Wang et al., 2001; Wang et al., 2002). Previous work has established that three members of the Pou4f family, including Pou4f1/Brn3a, Brn3b, and Pou4f3/Brn3c, participate in a combinatorial code of RGC type specification, in collaboration with several other TFs (Badea, Cahill, et al., 2009; Badea & Nathans, 2011; Shi et al., 2013). The three Brn3 factors are expressed in partially overlapping populations of RGC types, and regulate distinct morphological and molecular features of these cells, either alone or in combination. In addition, Pou4f/Brn3 TFs are also responsible for specifying other types of projection sensory neurons, involved in somatosensation, the vestibular and auditory senses (Badea et al., 2012; Erkman et al., 1996; Erkman et al., 2000; Gan et al., 1996; Wang et al., 2002; Xiang et al., 1997; Xiang, Gao, Hasson, & Shin, 1998).
In addition to transcriptional control, the development and specification of sensory neurons requires neurotrophic support, provided in large part by ligands from target derived neurotrophins (NTs) and glial derived neurotrophic factor (GDNF) families, and their receptors. Mice carrying loss of function mutations in a variety of neurotrophins or their receptors exhibit loss of sensory neuron populations or specific types (Airaksinen & Saarma, 2002; Ernsberger, 2008; Marmigere & Ernfors, 2007). The exact role of these neurotrophic factors in RGC development, however, is relatively poorly understood.