Publications

2023

 Mesenchymal Wnts are required for morphogenetic movements of calvarial osteoblasts during apical expansion.

Polsani N, Yung T, Thomas E, Phung-Rojas M, Gupta I, Denker J, Feng X, Ibarra B, Hopyan S, Atit RP. bioRxiv. 2023 Dec 7:2023.12.05.570300. doi: 10.1101/2023.12.05.570300. Preprint.

During apical expansion of the frontal bone primordia, non-canonical Wnts in the mesenchyme are required for morphogenetic movements of calvarial osteoblasts, cell elongation, cell polarity, and protrusive activity.  We found calvarial osteoblasts have convergent extension behavior in the basal portion of the primordia and protrusive activity more apically that is dependent on non-canonical Wnt signaling. 

Apical expansion of calvarial osteoblasts and suture patency is dependent on graded fibronectin cues.

Feng X, Molteni H, Gregory M, Lanza J, Polsani N, Wyetzner R, Hawkins MB, Holmes G, Hopyan S, Harris MP, Atit RP.bioRxiv. 2023 Jan 16:2023.01.16.524278. doi: 10.1101/2023.01.16.524278. Preprint.

Apical expansion of frontal bone primordia is dependent on graded expression of Fibronectin1 matrix protein.  Fibronectin1 substrate also promotes cellular elongation, actin enrichment and preserves suture patency of the coronal suture.  Calvarial osteoblasts use Wasl-dependent lamellipodia to migrate on Fibronectin1 substrate during apical expansion.  

2021

Skin fibrosis and recovery is dependent on Wnt activation via DPP4

Jussila AR, Zhang B, Caves E, Kirti S, Steele M, Hamburg-Shields E, Lydon J, Ying Y, Lafyatis R, Rajagopalan S, Horsley V, Atit RP. Skin fibrosis and recovery is dependent on Wnt activation via DPP4, The Journal of Investigative Dermatology (2021), doi: https://doi.org/10.1016/ 

Chart of skin fibrosis and recovery

Upon Wnt activation in the dermis and dermal white adipose tissue (DWAT), there is depletion of lipid filled adipocytes by 10days and increase in high density matrix and fiber thickness of collagen matrix and proteoglycans by 21 days.  Upon de-inducing Wnt activation, there is spontaneous reversal of fibrotic remodeling in dermis and DWAT.  In the absence of Dipeptidyl peptidase 4 (DPP4), the dermis and DWAT are rescued from Wnt activated fibrotic remodeling. This protection leads to preservation of skin architecture. 

Wnt-Dependent Activation of ERK Mediates Repression of Chondrocyte Fate during Calvarial Development

Ibarra BA, Machen C, Atit RP. Wnt-Dependent Activation of ERK Mediates Repression of Chondrocyte Fate during Calvarial Development. J Dev Biol. 2021 Jun 27;9(3):23. doi: 10.3390/jdb9030023. 

Canonical Wnt signaling transduction in the cranial mesenchyme
Canonical Wnt signaling transduction in the cranial mesenchyme sustains mesenchyme Wnt ligand expression and uses ERK1/2 signaling to promote calvarial osteoblast fate-program and inhibit cartilage fate-program.

Dermal EZH2 orchestrates dermal differentiation and epidermal proliferation during murine skin development

Thulabandu V, Nehila T, Ferguson JW, Atit RP. Dermal EZH2 orchestrates dermal differentiation and epidermal proliferation during murine skin development. Dev Biol. 2021 Oct;478:25-40. doi: 10.1016/j.ydbio.2021.06.008. Epub 2021 Jun 21. PMID: 34166654

Mouse embryonic skin development
Dermal Ezh2 controls expression of canonical Wnt/beta-catenin signaling in the dermis to specify dermal fate and regulate retinoic acid signaling for epidermal proliferation.

Polycomb Repressive Complex 2: a Dimmer Switch of Gene Regulation in Calvarial Bone Development

Nehila T, Ferguson JW, Atit RP. Polycomb Repressive Complex 2: a Dimmer Switch of Gene Regulation in Calvarial Bone Development. Curr Osteoporos Rep. 2020 Aug;18(4):378-387. doi: 10.1007/s11914-020-00603-5.PMID: 32748325 Review. 

Example of how PRC2 Knockout leads to subtle changes in gene expression
Epigenetic regulator, Polycomb Repressive Complex2 (PRC2) regulates expression of genes that function as activators and repressors, serving as a potential “rheostat” or “dimmer switch” for target gene expression. Deletion of the PRC2 core component, EZH2 can lead to numerous gene expression and can lead to smaller changes in target gene expression.

2019-2020

2018

2016-2017

2015

2012

2010

2003-2008