An evolving NGF-Hoxd1 signaling pathway mediates development of divergent neural circuits in vertebrates

Abstract

Summary Species are endowed with unique sensory capabilities encoded by divergent neural circuits. One potential explanation for how divergent circuits have evolved is that conserved extrinsic signals are differentially interpreted by developing neurons of different species to yield unique patterns of axonal connections. Although NGF controls survival, maturation and axonal projections of nociceptors of different vertebrates, whether the NGF signal is differentially transduced in different species to yield unique features of nociceptor circuits is unclear. We identified a species-specific signaling module induced by NGF and mediated by a rapidly evolving Hox transcription factor, Hoxd1. Mice lacking Hoxd1 display altered nociceptor circuitry which resembles that normally found in chicks. Conversely, ectopic expression of Hoxd1 in developing chick nociceptors promotes a pattern of axonal projections reminiscent of the mouse. We propose that conserved growth factors control divergent neuronal transcriptional events which mediate interspecies differences in neural circuits and the behaviors they control.

Development of oculomotor circuitry independent of hox3 genes

“…Only horizontal eye movement behavior was intermittently degraded by the activity of an ectopic circuit associated with the knockdown of hox3 . The contrasting level of Hox influence on neuronal identity and circuit formation in the auditory and oculomotor systems illustrates that the role of Hox genes in the hindbrain must be understood and interpreted on a case-by-case basis 3,18,36,52,53 .…”

“…This interpretation of the r5-6 organization is consistent with data from the mouse mutant kriesler 31 . Conventionally, the repertoire of neurons in a rhombomere after Hox perturbation has been explained by homeosis and/or a redundant activity of other Hox genes and their cofactors 3,8,52,62 . Specific combinations of Hox genes, the “Hox code”, have been proposed to determine neuronal identity and connectivity patterns 18,53 .…”

Molecular Control of the Neural Crest and Peripheral Nervous System Development

“…For example, mouse mutants that lack both Bax and NGF / TrkA do not exhibit a loss of sensory neurons; however, nociceptive neurons fail to innervate the peripheral cutaneous field (Patel et al, 2000). With this approach, the multifunctional effects of various trophic factors on target innervation, subtype specification, and synapse formation have been definitively evaluated (Deppmann et al, 2008; Glebova & Ginty, 2004; Guo et al, 2011; Luo et al, 2007; Patel et al, 2003; Sharma et al, 2010). …”

Modularity of CHIP/LDB transcription complexes regulates cell differentiation

“…) In addition to dissecting the mechanisms of transcription, many studies aim at unraveling the driving forces in the evolution of transcription. [12][13][14][15] experiments comparing transcriptional outputs between various fly species have contributed much to this field. In Drosophila, the enhancer trap procedure was used for identifying regulatory sequences in the genome and for characterizing their expression domains using reporter genes.…”