# The homeodomain transcription factor Phox2 in the stellate ganglion of the squid Loligo pealei

**Authors:** J. Peter H. Burbach, Anita J. C. G. M. Hellemons, Philip Grant, Harish C. Pant

PMC · DOI: 10.1242/bio.012476 · 2015-06-26

## TL;DR

This paper identifies a homeodomain transcription factor, lpPhox2, in the squid Loligo pealei and explores its role in neuronal development and function.

## Contribution

The study identifies the squid ortholog of Phox2a/b and shows its expression pattern and potential regulatory role in neuronal identity.

## Key findings

- lpPhox2 is expressed in the developing and adult stellate ganglion of squid, specifically in the giant fiber lobe.
- lpPhox2 shares homology with mammalian Phox2 only in the homeodomain and cannot transactivate the DBH promoter in mammalian cells.
- The Fmrf gene's upstream region contains potential Phox2a/b binding sites, suggesting regulatory interaction.

## Abstract

Homeodomain transcription factors regulate development of embryos and cellular physiology in adult systems. Paired-type homeodomain genes constitute a subclass that has been particularly implicated in establishment of neuronal identity in the mammalian nervous system. We isolated fragments of eight homeodomain genes of this subclass expressed in the stellate ganglion of the North Atlantic long finned squid Loligo pealei (lp) [Note: Loligo pealei has been officially renamed Doryteuthis pealei. For reasons of uniformity and clarity Loligo pealei (lp) is used here]. Of the most abundant ones, we cloned a full length cDNA which encoded the squid ortholog of the paired-type homeodomain proteins Phox2a/b. The homology of lpPhox2 to invertebrate and mammalian Phox2 was limited to the homeodomain. In contrast to mouse Phox2b, lpPhox2 was unable to transactivate the dopamine beta-hydroxylase (DBH) promoter in a heterologous mammalian transfection system. In vivo, lpPhox2 was expressed in the developing stellate ganglion of stage 27 squid embryos and continued to be expressed in the adult stellate neurons where expression was confined to the giant fiber lobe containing the neurons that form the giant axons. The expression of lpPhox was similarly timed and distributed as the Fmrf gene. Furthermore, the Fmrf upstream region contained putative Phox2a/b binding sites. These results suggest a role of lpPhox2 in the developmental specification of neuronal identity and regulation of neurons of the squid giant axon.

## Linked entities

- **Genes:** FMRFa (FMRFamide) [NCBI Gene 36030]
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** ZFHX4 (zinc finger homeobox 4) [NCBI Gene 79776] {aka ZFH4, ZHF4}, DBH (dopamine beta-hydroxylase) [NCBI Gene 1621] {aka DBM, ORTHYP1}, ARX (aristaless related homeobox) [NCBI Gene 170302] {aka CT121, EIEE1, ISSX, MRX29, MRX32, MRX33}, PITX3 (paired like homeodomain 3) [NCBI Gene 5309] {aka ASGD1, ASMD, ASOD, CTPP4, CTRCT11}, PHOX2A (paired like homeobox 2A) [NCBI Gene 401] {aka ARIX, CFEOM2, FEOM2, PMX2A}, GSC (goosecoid homeobox) [NCBI Gene 145258] {aka GSC1, SAMS}, ceh-17 (Homeobox protein ceh-17) [NCBI Gene 172059], unc-30 (Homeobox domain-containing protein;Homeobox protein unc-30) [NCBI Gene 178265], Bltp1 (bridge-like lipid transfer protein family member 1) [NCBI Gene 229227] {aka 4732443H21, 4932438A13Rik, B830039D19Rik, D630029K19Rik, FSA, Kiaa1109}, Dbh (dopamine beta hydroxylase) [NCBI Gene 13166], PITX2 (paired like homeodomain 2) [NCBI Gene 5308] {aka ARP1, ASGD4, Brx1, IDG2, IGDS, IGDS2}, TUBA1B (tubulin alpha 1b) [NCBI Gene 10376] {aka K-ALPHA-1}, Phox2a (paired-like homeobox 2a) [NCBI Gene 11859] {aka Arix, Phox2, Pmx2, Pmx2a, Px2a}, RPF1 (ribosome production factor 1 homolog) [NCBI Gene 80135] {aka BXDC5}, PHOX2B (paired like homeobox 2B) [NCBI Gene 8929] {aka CCHS, NBLST2, NBPhox, PMX2B}, Phox2b (paired-like homeobox 2b) [NCBI Gene 18935] {aka Dilp1, NBPhox, Pmx2b, Px2b}
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Xenopus laevis (African clawed frog, species) [taxon 8355], Ciona intestinalis (sea vase, species) [taxon 7719], Sepia officinalis (common cuttlefish, species) [taxon 6610], Aplysia californica (California sea hare, species) [taxon 6500], Drosophila melanogaster (fruit fly, species) [taxon 7227], C. elegans [taxon 328850], Lottia gigantea (owl limpet, species) [taxon 225164], Doryteuthis pealeii (longfin inshore squid, species) [taxon 1051067], Mnemiopsis leidyi (American comb jelly, species) [taxon 27923], Euprymna scolopes (species) [taxon 6613], Homo sapiens (human, species) [taxon 9606], Rattus norvegicus (brown rat, species) [taxon 10116], Lymnaea stagnalis (great pond snail, species) [taxon 6523]
- **Cell lines:** pSG5 — Mus musculus (Mouse), Transformed cell line (CVCL_5U93), Neuro2A — Mus musculus (Mouse), Mouse neuroblastoma, Cancer cell line (CVCL_0470)

## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC4542286/full.md

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Source: https://tomesphere.com/paper/PMC4542286