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Cell signaling regulation in salivary gland development

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Abstract

The mammalian salivary gland develops as a highly branched structure designed to produce and secrete saliva. This review focuses on research conducted on mammalian salivary gland development, particularly on the differentiation of acinar, ductal, and myoepithelial cells. We discuss recent studies that provide conceptual advances in the understanding of the molecular mechanisms of salivary gland development. In addition, we describe the organogenesis of submandibular glands (SMGs), model systems used for the study of SMG development, and the key signaling pathways as well as cellular processes involved in salivary gland development. The findings from the recent studies elucidating the identity of stem/progenitor cells in the SMGs, and the process by which they are directed along a series of cell fate decisions to form functional glands, are also discussed. Advances in genetic tools and tissue engineering strategies will significantly increase our knowledge about the mechanisms by which signaling pathways and cells establish tissue architecture and function during salivary gland development, which may also be conserved in the growth and development of other organ systems. An increased knowledge of organ development mechanisms will have profound implications in the design of therapies for the regrowth or repair of injured tissues. In addition, understanding how the processes of cell survival, expansion, specification, movement, and communication with neighboring cells are regulated under physiological and pathological conditions is critical to the development of future treatments.

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Abbreviations

SOX9:

Sex-determining region Y-box 9

KIT:

KIT proto-oncogene, receptor tyrosine kinase

FGF:

Fibroblast growth factor

TGF-β:

Transforming growth factor-β

SMGs:

Submandibular glands

SLGs:

Sublingual glands

PGs:

Parotid glands

KRT19+ :

Keratin 19 positive

MYC:

Myelocytomatosis oncogene

KIT:

KIT proto-oncogene, receptor tyrosine kinase

AKT:

AKT serine/threonine kinase

PI3K:

Phosphatidylinositol 3-kinase

EDA/EDAR:

Ectodysplasin-A/ectodysplasin-A receptor

MAPK:

Mitogen-activated kinase-like protein

HS:

Heparan sulfate

ECM:

Extracellular matrix

SHH:

Sonic hedgehog

NRG:

Neuregulin

HH:

Hedgehog

SMO:

Smoothened

PTCH:

Patched

BMP:

Bone morphogenetic proteins

GDNF:

Glial cell line-derived neurotrophic growth factor

NRTN:

Neurturin

Ach:

Acetylcholine

VIP:

Vasoactive intestinal peptide

Ascl3:

Achaete-scute homolog 3

SCF:

Stem cell factor

AQP:

Aquaporin

ID:

Intercalated duct

SD:

Striated duct

ED:

Excretory duct

NRF2:

NF-E2-related factor 2

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Acknowledgments

This study was supported by grants from the National Institute of Dental and Craniofacial Research, NIH (DE026509, DE026767, DE028340, and DE029818), and UTHealth School of Dentistry faculty funds to JI.

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  1. Department of Diagnostic and Biomedical Sciences, School of Dentistry, The University of Texas Health Science Center at Houston (UTHealth), 1941 East Road, BBS 4208, Houston, TX, 77054, USA

    Akiko Suzuki, Kenichi Ogata & Junichi Iwata

  2. Center for Craniofacial Research, UTHealth, Houston, TX, 77054, USA

    Akiko Suzuki, Kenichi Ogata & Junichi Iwata

  3. Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan

    Kenichi Ogata

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Suzuki, A., Ogata, K. & Iwata, J. Cell signaling regulation in salivary gland development. Cell. Mol. Life Sci. 78, 3299–3315 (2021). https://doi.org/10.1007/s00018-020-03741-2

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