Retinoic acid influences anteroposterior positioning of epidermal sensory neurons and their gene expression in a developing chordate (amphioxus)

Abstract

In developing chordates, retinoic acid (RA) signaling patterns the rostrocaudal body axis globally and affects gene expression locally in some differentiating cell populations. Here we focus on development of epidermal sensory neurons in an invertebrate chordate (amphioxus) to determine how RA signaling influences their rostrocaudal distribution and gene expression (for AmphiCoe, a neural precursor gene; for amphioxus islet and AmphiERR, two neural differentiation genes; and for AmphiHox1, -3, -4, and -6). Treatments with RA or an RA antagonist (BMS009) shift the distribution of developing epidermal neurons anteriorly or posteriorly, respectively. These treatments also affect gene expression patterns in the epidermal neurons, suggesting that RA levels may influence specification of neuronal subtypes. Although colinear expression of Hox genes is well known for the amphioxus central nervous system, we find an unexpected comparable colinearity for AmphiHox1, -3, -4, and -6 in the developing epidermis; moreover, RA levels affect the anteroposterior extent of these Hox expression domains, suggesting that RA signaling controls a colinear Hox code for anteroposterior patterning of the amphioxus epidermis. Thus, in amphioxus, the developing peripheral nervous system appears to be structured by mechanisms parallel to those that structure the central nervous system. One can speculate that, during evolution, an ancestral deuterostome that structured its panepidermal nervous system with an RA-influenced Hox code gave rise to chordates in which this patterning mechanism persisted within the epidermal elements of the peripheral nervous system and was transferred to the neuroectoderm as the central nervous system condensed dorsally.

Retinoic acid signaling in development: Tissue‐specific functions and evolutionary origins

“…During normal development, these cells are scattered along the entire AP axis of the developing general ectoderm and express a combinatorial code of different proneural genes including coe, islet, and err. Treatments with RA and RA antagonist shift the AP distribution of sensory neurons in the general ectoderm and alter the combinatorial code of proneural genes expressed in these cells (Schubert et al, 2004). The effect of RA on the distribution of sensory neurons in the amphioxus general ectoderm is reminiscent of the posteriorizing action of exogenous RA on the lateral line neurons of axolotls (Gibbs and Northcutt, 2004).…”

“…Thus, while exogenous RA shifts collinear expression of hox genes anteriorly, RA antagonist treatment downregulates transcription of hox genes in the general ectoderm. Moreover, Schubert et al (2004) demonstrated that in the amphioxus general ectoderm the differentiation of sensory neurons is sensitive to RA signals. During normal development, these cells are scattered along the entire AP axis of the developing general ectoderm and express a combinatorial code of different proneural genes including coe, islet, and err.…”

“…In amphioxus, the other group of invertebrate chordates, RA signaling in the general ectoderm controls collinear expression of hox genes as well as specification of neuronal subtypes (Schubert et al, 2004) (see Fig. 3).…”

Conserved RARE localization in amphioxusHox clusters and implications forHox code evolution in the vertebrate neural crest

“…In order to determine the evolution of the neural crest Hox code, we must also find out how DR5 elements are involved in transcriptional regulation of amphioxus Hox. Schubert et al (2004) demonstrated that AmphiHox1, 3, and 4 expression are sensitive to exogenous RA in both the neural tube and epidermis. We are currently investigating how RAREs are involved in expression of the neural tube and epidermis of ascidian and amphioxus embryos.…”

Retinoic acid-driven Hox1 is required in the epidermis for forming the otic/atrial placodes during ascidian metamorphosis

“…In addition, this network functions directly in the ASP/otic placode to pattern it. Similarly, in amphioxus, RA functions in patterning of the epidermal sensory organ (Schubert et al, 2004), from which placodes are thought to originate (Holland and Holland, 2001). In vertebrates, otic placode formation depends on signals from a properly patterned CNS (Hans and Westerfield, 2007), and is therefore indirectly dependent on RA and Hox1.…”