Wnt7A Identifies Embryonic γ-motor Neurons and Reveals Early Postnatal Dependence of γ-motor Neurons on a Muscle Spindle-derived Signal

Overview

Journal J Neurosci

Specialty Neurology

Date 2012 Jun 23

PMID 22723712

Citations 24

Authors

Soha Ashrafi

Melanie Lalancette-Hebert

Andreas Friese

Markus Sigrist

Silvia Arber

Neil A Shneider

Julia A Kaltschmidt

Affiliations

Soon will be listed here.

Abstract

Motor pools comprise a heterogeneous population of motor neurons that innervate distinct intramuscular targets. While the organization of motor neurons into motor pools has been well described, the time course and mechanism of motor pool diversification into functionally distinct classes remains unclear. γ-Motor neurons (γ-MNs) and α-motor neurons (α-MNs) differ in size, molecular identity, synaptic input and peripheral target. While α-MNs innervate extrafusal skeletal muscle fibers to mediate muscle contraction, γ-MNs innervate intrafusal fibers of the muscle spindle, and regulate sensitivity of the muscle spindle in response to stretch. In this study, we find that the secreted signaling molecule Wnt7a is selectively expressed in γ-MNs in the mouse spinal cord by embryonic day 17.5 and continues to molecularly distinguish γ-from α-MNs into the third postnatal week. Our data demonstrate that Wnt7a is the earliest known γ-MN marker, supporting a model of developmental divergence between α- and γ-MNs at embryonic stages. Furthermore, using Wnt7a expression as an early marker of γ-MN identity, we demonstrate a previously unknown dependence of γ-MNs on a muscle spindle-derived, GDNF-independent signal during the first postnatal week.

Citing Articles

Molecular, Morphological and Electrophysiological Differences between Alpha and Gamma Motoneurons with Special Reference to the Trigeminal Motor Nucleus of Rat.

Kang Y, Saito M, Toyoda H Int J Mol Sci. 2024; 25(10).

PMID: 38791305 PMC: 11121624. DOI: 10.3390/ijms25105266.

Single-cell transcriptomic landscape of the developing human spinal cord.

Andersen J, Thom N, Shadrach J, Chen X, Onesto M, Amin N Nat Neurosci. 2023; 26(5):902-914.

PMID: 37095394 DOI: 10.1038/s41593-023-01311-w.

Intrafusal-fiber LRP4 for muscle spindle formation and maintenance in adult and aged animals.

Cao R, Chen P, Wang H, Jing H, Zhang H, Xing G Nat Commun. 2023; 14(1):744.

PMID: 36765071 PMC: 9918736. DOI: 10.1038/s41467-023-36454-8.

Methodological advances for studying gamma motor neurons.

Wilkinson K Curr Opin Physiol. 2022; 19:135-140.

PMID: 36561377 PMC: 9770680. DOI: 10.1016/j.cophys.2020.10.002.

ERR2 and ERR3 promote the development of gamma motor neuron functional properties required for proprioceptive movement control.

Khan M, Cherukuri P, Negro F, Rajput A, Fabrowski P, Bansal V PLoS Biol. 2022; 20(12):e3001923.

PMID: 36542664 PMC: 9815657. DOI: 10.1371/journal.pbio.3001923.

References

Yang X, Arber S, William C, Li L, Tanabe Y, Jessell T . Patterning of muscle acetylcholine receptor gene expression in the absence of motor innervation. Neuron. 2001; 30(2):399-410. DOI: 10.1016/s0896-6273(01)00287-2. View

Wichterle H, Lieberam I, Porter J, Jessell T . Directed differentiation of embryonic stem cells into motor neurons. Cell. 2002; 110(3):385-97. DOI: 10.1016/s0092-8674(02)00835-8. View

Peljto M, Dasen J, Mazzoni E, Jessell T, Wichterle H . Functional diversity of ESC-derived motor neuron subtypes revealed through intraspinal transplantation. Cell Stem Cell. 2010; 7(3):355-66. PMC: 2933095. DOI: 10.1016/j.stem.2010.07.013. View

Parr B, McMahon A . Dorsalizing signal Wnt-7a required for normal polarity of D-V and A-P axes of mouse limb. Nature. 1995; 374(6520):350-3. DOI: 10.1038/374350a0. View

Chakkalakal J, Nishimune H, Ruas J, Spiegelman B, Sanes J . Retrograde influence of muscle fibers on their innervation revealed by a novel marker for slow motoneurons. Development. 2010; 137(20):3489-99. PMC: 2947760. DOI: 10.1242/dev.053348. View

Lin J, Saito T, Anderson D, Lance-Jones C, Jessell T, Arber S . Functionally related motor neuron pool and muscle sensory afferent subtypes defined by coordinate ETS gene expression. Cell. 1998; 95(3):393-407. DOI: 10.1016/s0092-8674(00)81770-5. View

Luo W, Enomoto H, Rice F, Milbrandt J, Ginty D . Molecular identification of rapidly adapting mechanoreceptors and their developmental dependence on ret signaling. Neuron. 2010; 64(6):841-56. PMC: 2813518. DOI: 10.1016/j.neuron.2009.11.003. View

Jessell T . Neuronal specification in the spinal cord: inductive signals and transcriptional codes. Nat Rev Genet. 2001; 1(1):20-9. DOI: 10.1038/35049541. View

Livet J, Sigrist M, Stroebel S, de Paola V, Price S, Henderson C . ETS gene Pea3 controls the central position and terminal arborization of specific motor neuron pools. Neuron. 2002; 35(5):877-92. DOI: 10.1016/s0896-6273(02)00863-2. View

10.

ROMANES G . The motor cell columns of the lumbo-sacral spinal cord of the cat. J Comp Neurol. 1951; 94(2):313-63. DOI: 10.1002/cne.900940209. View

11.

Hippenmeyer S, Vrieseling E, Sigrist M, Portmann T, Laengle C, Ladle D . A developmental switch in the response of DRG neurons to ETS transcription factor signaling. PLoS Biol. 2005; 3(5):e159. PMC: 1084331. DOI: 10.1371/journal.pbio.0030159. View

12.

Lamballe F, Genestine M, Caruso N, Arce V, Richelme S, Helmbacher F . Pool-specific regulation of motor neuron survival by neurotrophic support. J Neurosci. 2011; 31(31):11144-58. PMC: 6623376. DOI: 10.1523/JNEUROSCI.2198-11.2011. View

13.

Kanning K, Kaplan A, Henderson C . Motor neuron diversity in development and disease. Annu Rev Neurosci. 2010; 33:409-40. DOI: 10.1146/annurev.neuro.051508.135722. View

14.

Arber S, Han B, Mendelsohn M, Smith M, Jessell T, Sockanathan S . Requirement for the homeobox gene Hb9 in the consolidation of motor neuron identity. Neuron. 1999; 23(4):659-74. DOI: 10.1016/s0896-6273(01)80026-x. View

15.

Tourtellotte W, Milbrandt J . Sensory ataxia and muscle spindle agenesis in mice lacking the transcription factor Egr3. Nat Genet. 1998; 20(1):87-91. DOI: 10.1038/1757. View

16.

Enomoto H, Hughes I, Golden J, Baloh R, Yonemura S, Heuckeroth R . GFRalpha1 expression in cells lacking RET is dispensable for organogenesis and nerve regeneration. Neuron. 2004; 44(4):623-36. DOI: 10.1016/j.neuron.2004.10.032. View

17.

Vrieseling E, Arber S . Target-induced transcriptional control of dendritic patterning and connectivity in motor neurons by the ETS gene Pea3. Cell. 2006; 127(7):1439-52. DOI: 10.1016/j.cell.2006.10.042. View

18.

Hippenmeyer S, Shneider N, Birchmeier C, Burden S, Jessell T, Arber S . A role for neuregulin1 signaling in muscle spindle differentiation. Neuron. 2002; 36(6):1035-49. DOI: 10.1016/s0896-6273(02)01101-7. View

19.

Friese A, Kaltschmidt J, Ladle D, Sigrist M, Jessell T, Arber S . Gamma and alpha motor neurons distinguished by expression of transcription factor Err3. Proc Natl Acad Sci U S A. 2009; 106(32):13588-93. PMC: 2716387. DOI: 10.1073/pnas.0906809106. View

20.

Sabharwal P, Lee C, Park S, Rao M, Sockanathan S . GDE2 regulates subtype-specific motor neuron generation through inhibition of Notch signaling. Neuron. 2011; 71(6):1058-70. PMC: 3183458. DOI: 10.1016/j.neuron.2011.07.028. View