Desert hedgehog protein (DHH) is a crucial signaling molecule involved in various developmental processes and disease conditions. DHH, along with its receptor Patched (PTCH1), regulates the proper development of myoid cells in the peritubular region and fetal Leydig cells in the interstitial region [1]. It is also associated with the progression of stomach adenocarcinoma by regulating the Hedgehog signaling pathway [2]. Furthermore, DHH plays a significant role in specifying fetal Leydig cell fate in testis organogenesis and the differentiation of peritubular myoid cells, thereby contributing to the formation of testis cords [3]. Additionally, DHH is essential for the formation of adult-type Leydig cells and the normal development of peritubular cells and seminiferous tubules in the mouse testis [4].
Moreover, DHH is implicated in genetic disorders such as 46,XY complete pure gonadal dysgenesis and minifascicular neuropathy [5][6]. It is also known to be a negative regulator of CD44-CD25+ double negative T lymphocytes developmental stage in thymic differentiation [7]. Furthermore, DHH has been linked to autism spectrum disorder, as its serum levels have been preliminarily associated with this condition [8].
In terms of its molecular characteristics, DHH is one of the three highly conserved hedgehog genes in mammals, along with Sonic hedgehog (SHH) and Indian hedgehog (IHH) [9]. These hedgehog proteins are capable of binding to PTCH1, leading to signal transduction via derepression of the co-receptor, SMO [10]. Additionally, DHH proteins function in cell-cell contact-mediated juxtacrine signaling, unlike SHH, which highlights its distinct mechanisms of action [10].
References:
[1] H. Yao, W. Whoriskey, & B. Capel, "Desert hedgehog/patched 1 signaling specifies fetal leydig cell fate in testis organogenesis", Genes & Development, vol. 16, no. 11, p. 1433-1440, 2002. https://doi.org/10.1101/gad.981202
[2] B. Liu, "Pknox1 acts as a transcription factor of dhh and promotes the progression of stomach adenocarcinoma by regulating the hedgehog signalling pathway", International Journal of Immunopathology and Pharmacology, vol. 37, 2023. https://doi.org/10.1177/03946320231208833
[3] A. Clark, K. Garland, & L. Russell, "Desert hedgehog (dhh) gene is required in the mouse testis for formation of adult-type leydig cells and normal development of peritubular cells and seminiferous tubules", Biology of Reproduction, vol. 63, no. 6, p. 1825-1838, 2000. https://doi.org/10.1095/biolreprod63.6.1825
[4] P. Canto, D. Söderlund, E. Reyes, & J. Méndez, "Mutations in the desert hedgehog (dhh) gene in patients with 46,xy complete pure gonadal dysgenesis", The Journal of Clinical Endocrinology & Metabolism, vol. 89, no. 9, p. 4480-4483, 2004. https://doi.org/10.1210/jc.2004-0863
[5] N. Sato, R. Maekawa, H. Ishiura, J. Mitsui, H. Naruse, S. Tokushigeet al., "Partial duplication of dhh causes minifascicular neuropathy", Annals of Clinical and Translational Neurology, vol. 4, no. 6, p. 415-421, 2017. https://doi.org/10.1002/acn3.417
[6] S. Kariuki, "Desert hedgehog is a negative regulator of cd44-cd25+ double negative t lymphocytes developmental stage in thymic differentiation", International Journal of Research in Medical Sciences, vol. 6, no. 3, p. 734, 2018. https://doi.org/10.18203/2320-6012.ijrms20180586
[7] S. Bashir, D. Halepoto, & L. Al-Ayadhi, "Serum level of desert hedgehog protein in autism spectrum disorder: preliminary results", Medical Principles and Practice, vol. 23, no. 1, p. 14-17, 2013. https://doi.org/10.1159/000354295
[8] R. Pola, L. Ling, T. Aprahamian, E. Barban, M. Bosch–Marcé, C. Curryet al., "Postnatal recapitulation of embryonic hedgehog pathway in response to skeletal muscle ischemia", Circulation, vol. 108, no. 4, p. 479-485, 2003. https://doi.org/10.1161/01.cir.0000080338.60981.fa
[9] L. Spicer, S. Sudo, P. Aad, L. Wang, S. Chun, I. Ben-Shlomoet al., "The hedgehog-patched signaling pathway and function in the mammalian ovary: a novel role for hedgehog proteins in stimulating proliferation and steroidogenesis of theca cells", Reproduction, vol. 138, no. 2, p. 329-339, 2009. https://doi.org/10.1530/rep-08-0317
[10] K. Ayers, J. Bergen, G. Robevska, N. Listyasari, J. Raza, I. Attaet al., "Functional analysis of novel desert hedgehog gene variants improves the clinical interpretation of genomic data and provides a more accurate diagnosis for patients with 46,xy differences of sex development", Journal of Medical Genetics, vol. 56, no. 7, p. 434-443, 2019. https://doi.org/10.1136/jmedgenet-2018-105893
