HeyL Regulates the Number of TrkC Neurons in Dorsal Root Ganglia

Overview

Journal Dev Biol

Publisher Elsevier

Specialties Biology
Reproductive Medicine

Date 2009 Jul 28

PMID 19631204

Citations 11

Authors

Abhishek Mukhopadhyay

Jennifer Jarrett

Timothy Chlon

John A Kessler

Affiliations

Soon will be listed here.

Abstract

The basic-helix-loop-helix transcription factor HeyL is expressed at high levels by neural crest progenitor cells (NCPs) that give rise to neurons and glia in dorsal root ganglia (DRG). Since HeyL expression was observed in these NCPs during the period of neurogenesis, we generated HeyL null mutants to help examine the factor's role in ganglion neuronal specification. Homozygous null mutation of HeyL reduced the number of TrkC(+) neurons in DRG at birth including the subpopulation that expresses the ETS transcription factor ER81. Conversely, null mutation of the Hey paralog, Hey1, increased the number of TrkC(+) neurons. Null mutation of HeyL increased expression of the Hey paralogs Hey1 and Hey2, suggesting that HeyL normally inhibits their expression. Double null mutation of both Hey1 and HeyL rescued TrkC(+) neuron numbers to control levels. Thus, the balance between HeyL and Hey1 expression regulates the differentiation of a subpopulation of TrkC(+) neurons in the DRG.

Citing Articles

Adult Neurogenesis of the Medial Geniculate Body: In Vitro and Molecular Genetic Analyses Reflect the Neural Stem Cell Capacity of the Rat Auditory Thalamus over Time.

Engert J, Spahn B, Sommerer S, Ehret Kasemo T, Hackenberg S, Rak K Int J Mol Sci. 2024; 25(5).

PMID: 38473870 PMC: 10932413. DOI: 10.3390/ijms25052623.

Cleaved Delta like 1 intracellular domain regulates neural development via Notch signal-dependent and -independent pathways.

Okubo Y, Ohtake F, Igarashi K, Yasuhiko Y, Hirabayashi Y, Saga Y Development. 2021; 148(19).

PMID: 34519339 PMC: 8513606. DOI: 10.1242/dev.193664.

The notch target gene HEYL modulates metastasis forming capacity of colorectal cancer patient-derived spheroid cells in vivo.

Weber S, Koschade S, Hoffmann C, Dubash T, Giessler K, Dieter S BMC Cancer. 2019; 19(1):1181.

PMID: 31796022 PMC: 6892194. DOI: 10.1186/s12885-019-6396-4.

Spatial and temporal patterns of gene expression during neurogenesis in the sea urchin .

Slota L, Miranda E, McClay D Evodevo. 2019; 10:2.

PMID: 30792836 PMC: 6371548. DOI: 10.1186/s13227-019-0115-8.

Cortical interlaminar astrocytes across the therian mammal radiation.

Falcone C, Wolf-Ochoa M, Amina S, Hong T, Vakilzadeh G, Hopkins W J Comp Neurol. 2018; 527(10):1654-1674.

PMID: 30552685 PMC: 6465161. DOI: 10.1002/cne.24605.

References

Steidl C, Leimeister C, Klamt B, Maier M, Nanda I, Dixon M . Characterization of the human and mouse HEY1, HEY2, and HEYL genes: cloning, mapping, and mutation screening of a new bHLH gene family. Genomics. 2000; 66(2):195-203. DOI: 10.1006/geno.2000.6200. View

Satow T, Bae S, Inoue T, Inoue C, MIYOSHI G, Tomita K . The basic helix-loop-helix gene hesr2 promotes gliogenesis in mouse retina. J Neurosci. 2001; 21(4):1265-73. PMC: 6762251. View

Hirata H, Tomita K, Bessho Y, Kageyama R . Hes1 and Hes3 regulate maintenance of the isthmic organizer and development of the mid/hindbrain. EMBO J. 2001; 20(16):4454-66. PMC: 125583. DOI: 10.1093/emboj/20.16.4454. View

Ishibashi M, Ang S, Shiota K, Nakanishi S, Kageyama R, Guillemot F . Targeted disruption of mammalian hairy and Enhancer of split homolog-1 (HES-1) leads to up-regulation of neural helix-loop-helix factors, premature neurogenesis, and severe neural tube defects. Genes Dev. 1995; 9(24):3136-48. DOI: 10.1101/gad.9.24.3136. View

Kim J, Anderson D, Kintner C . Hes6 acts in a positive feedback loop with the neurogenins to promote neuronal differentiation. Development. 2000; 127(19):4203-16. DOI: 10.1242/dev.127.19.4203. View

Akazawa C, Sasai Y, Nakanishi S, Kageyama R . Molecular characterization of a rat negative regulator with a basic helix-loop-helix structure predominantly expressed in the developing nervous system. J Biol Chem. 1992; 267(30):21879-85. View

Fischer A, Steidl C, Wagner T, Lang E, Jakob P, Friedl P . Combined loss of Hey1 and HeyL causes congenital heart defects because of impaired epithelial to mesenchymal transition. Circ Res. 2007; 100(6):856-63. DOI: 10.1161/01.RES.0000260913.95642.3b. View

Nakagawa O, Nakagawa M, Richardson J, Olson E, Srivastava D . HRT1, HRT2, and HRT3: a new subclass of bHLH transcription factors marking specific cardiac, somitic, and pharyngeal arch segments. Dev Biol. 1999; 216(1):72-84. DOI: 10.1006/dbio.1999.9454. View

Mu X, Silos-Santiago I, Carroll S, Snider W . Neurotrophin receptor genes are expressed in distinct patterns in developing dorsal root ganglia. J Neurosci. 1993; 13(9):4029-41. PMC: 6576438. View

10.

Kokubo H, Miyagawa-Tomita S, Nakazawa M, Saga Y, Johnson R . Mouse hesr1 and hesr2 genes are redundantly required to mediate Notch signaling in the developing cardiovascular system. Dev Biol. 2005; 278(2):301-9. DOI: 10.1016/j.ydbio.2004.10.025. View

11.

ISO T, Sartorelli V, Chung G, Shichinohe T, Kedes L, Hamamori Y . HERP, a new primary target of Notch regulated by ligand binding. Mol Cell Biol. 2001; 21(17):6071-9. PMC: 87324. DOI: 10.1128/MCB.21.17.6071-6079.2001. View

12.

Leimeister C, Schumacher N, Steidl C, Gessler M . Analysis of HeyL expression in wild-type and Notch pathway mutant mouse embryos. Mech Dev. 2000; 98(1-2):175-8. DOI: 10.1016/s0925-4773(00)00459-7. View

13.

Huang E, Zang K, Schmidt A, Saulys A, Xiang M, Reichardt L . POU domain factor Brn-3a controls the differentiation and survival of trigeminal neurons by regulating Trk receptor expression. Development. 1999; 126(13):2869-82. PMC: 2710123. DOI: 10.1242/dev.126.13.2869. View

14.

Snider W . Functions of the neurotrophins during nervous system development: what the knockouts are teaching us. Cell. 1994; 77(5):627-38. DOI: 10.1016/0092-8674(94)90048-5. View

15.

Carroll S, Silos-Santiago I, Frese S, Ruit K, Milbrandt J, Snider W . Dorsal root ganglion neurons expressing trk are selectively sensitive to NGF deprivation in utero. Neuron. 1992; 9(4):779-88. DOI: 10.1016/0896-6273(92)90040-k. View

16.

Nakagawa O, McFADDEN D, Nakagawa M, Yanagisawa H, Hu T, Srivastava D . Members of the HRT family of basic helix-loop-helix proteins act as transcriptional repressors downstream of Notch signaling. Proc Natl Acad Sci U S A. 2000; 97(25):13655-60. PMC: 17631. DOI: 10.1073/pnas.250485597. View

17.

Carr P, Yamamoto T, Karmy G, Baimbridge K, Nagy J . Parvalbumin is highly colocalized with calbindin D28k and rarely with calcitonin gene-related peptide in dorsal root ganglia neurons of rat. Brain Res. 1989; 497(1):163-70. DOI: 10.1016/0006-8993(89)90983-9. View

18.

Leimeister C, Externbrink A, Klamt B, Gessler M . Hey genes: a novel subfamily of hairy- and Enhancer of split related genes specifically expressed during mouse embryogenesis. Mech Dev. 1999; 85(1-2):173-7. DOI: 10.1016/s0925-4773(99)00080-5. View

19.

Gratton M, Torban E, Jasmin S, Theriault F, German M, Stifani S . Hes6 promotes cortical neurogenesis and inhibits Hes1 transcription repression activity by multiple mechanisms. Mol Cell Biol. 2003; 23(19):6922-35. PMC: 193938. DOI: 10.1128/MCB.23.19.6922-6935.2003. View

20.

Gessler M, Knobeloch K, Helisch A, Amann K, Schumacher N, Rohde E . Mouse gridlock: no aortic coarctation or deficiency, but fatal cardiac defects in Hey2 -/- mice. Curr Biol. 2002; 12(18):1601-4. DOI: 10.1016/s0960-9822(02)01150-8. View