Biology subjects

Birjandi, A. A.

Publications and source records attributed to Birjandi, A. A..

3 recordsLinked to original sources

bioRxiv2023

Opto-lipidomics of tissues

Lipid metabolism and signalling play pivotal functions in biology and disease development. Despite this, there is currently no optical technique available that can directly visualise the lipidome in tissues. In this study, we introduce opto-lipidomics, a new approach to optical molecular tissue imaging. We expand the capability of vibrational Raman spectroscopy to identify individual lipids in complex tissue matrices through correlation with desorption electrospray ionisation (DESI) - mass spectrometry imaging in an integrated instrument. A computational pipeline of inter-modality regression analysis is established to extract lipidomic information from optical vibrational spectra. Opto-lipidomic imaging of transient cerebral ischemia-reperfusion injury in a murine model of ischemic stroke demonstrates the visualisation and identification of lipids in disease with unprecedented molecular specificity using light. Furthermore, we deploy opto-lipidomics in a handheld fiber-optic Raman probe and demonstrate real-time classification of bulk brain tissues based on specific lipid abundances. Opto-lipidomics opens a host of opportunities to study lipid biomarkers for diagnostics, prognostics, and novel therapeutic targets.

bioengineering↗

bioRxiv2020

Hedgehog signalling regulates patterning of the murine and human dentitions through Gas1 co-receptor function

The mammalian dentition exhibits wide numerical and morphological variation between different species. The regulation of dental pattern is achieved through complex reiterative molecular signalling interactions that occur through multiple stages of tooth development. We show that mice with loss-of-function in the Hedgehog co-receptor Gas1 have variation in size, morphology and number of teeth within the molar dentition. Specifically, premolar-like supernumerary teeth are present with high penetrance, arising through survival and continued development of vestigial tooth germs. We further demonstrate that Gas1 function in cranial neural crest cells is essential for the regulation of tooth number, acting to restrict Wnt signalling in vestigial tooth germs through facilitation of Shh signalling. Moreover, regulation of tooth number is independent of the additional Hedgehog co-receptors Cdon and Boc. Interestingly, further reduction of Shh pathway activity in a Gas1 mutant background leads to fusion of the molar field and ultimately, developmental arrest of tooth development rather than exacerbating the supernumerary phenotype. Finally, we demonstrate defective coronal morphology in the molar dentition of human subjects carrying GAS1 missense mutations, suggesting that regulation of Hedgehog signalling through GAS1 is also essential for normal patterning of the human dentition.

developmental biology↗

bioRxiv2017

Sonic hedgehog is required for neural crest-dependent patterning of the intrinsic tongue musculature

The tongue is a highly specialized muscular organ important for breathing, speech, taste and swallowing. The secreted signaling molecule Sonic hedgehog (Shh) is expressed in dorsal tongue epithelium from the initial developmental stage. In this study, we utilized a series of genetic approaches to investigate the role of Shh during mouse tongue formation. Temporal-specific global deletion of Shh demonstrated a functional requirement for normal patterning of the intrinsic tongue muscles and establishment of the lingual tendon. These defects were reproduced in the mutant with a specific loss of signaling in oropharyngeal epithelium by a Shh cis-enhancer. In these mutants, Ptch1 was lost in the underlying cranial neural crest (CNC)-derived mesenchymal lineage. The importance of Shh was confirmed by generating tissue-specific deletions in the ciliopathy gene Ofd1, which transduces Shh signaling. These results revealed Shh roles in patterning of the mesodermal intrinsic tongue muscles through CNC-derived mesenchyme, including the lingual tendon.

developmental biology↗