Ulrika Marklund Group
The Marklund laboratory focuses on neural cell diversity in the Enteric Nervous System (ENS). By determining the variety of ENS cell subtypes, the functions they normally serve and developmental specification, the group aims to improve diagnostic and therapeutic principles for gut disorders. The lab addresses these basic but critical questions by transcriptome analysis coupled with viral-based activity/gene manipulations using the mouse model.
Formation and function of neural subtypes in the Enteric Nervous System (ENS)
Unique amongst visceral organs, the gastrointestinal tract contains an own intrinsic nervous system. This so-called enteric nervous system (ENS) is the largest and most complex part of the peripheral nervous system and provides the gut autonomous control of peristalsis, blood flow and secretion. An even broader functional significance of the ENS is being recognized through its communication with the brain, immune system and microbiome. ENS dysfunction has been associated with many disorders including Hirschsprung disease, achalasia and Parkinson's disease. Despite the essential role of ENS in gut physiology and disease, the variety of functionally distinct neurons and how they specify during development is not known. By applying single cell transcriptome analysis we have recently established a new classification of enteric neuron subtypes and a mechanistic mode for how these neuron identities emerge. The new data sets allow refined experiments on ENS function and development, previously not possible.
My lab addresses fundamental questions in ENS neurobiology with the aim to: 1) dissect the precise connectivity and function of molecularly defined enteric neuron classes and 2) uncover the regulatory mechanisms and molecular programs that control neuronal cell fate decisions and differentiation in the developing ENS. We use a wide range of methodologies including transcriptome profiling, histochemical expression analysis, viral-mediated tracing and manipulation, mutant mice, functional in vivo assays and gene-editing in developing ENS. By resolving the ENS cell connectome and its development, we hope to pave the way for better understanding, characterization and treatment of prevalent gut disorders.
If you would be interested to join the lab as a Postdoc or Master student, please send a request by email (Ulrika.Marklund@ki.se) including a short CV and a description of your research interests.
Diversification of molecularly defined myenteric neuron classes revealed by single cell RNA-sequencing
Morarach K*, Mikhailova A*, Knoflach V, Memic F, Kumar R, Li W, Ernfors P, Marklund U#
BioRxiv 2020. doi: doi.org/10.1101/2020.03.02.955757
Molecular Architecture of the Mouse Nervous System.
Zeisel A, Hochgerner H, Lönnerberg P, Johnsson A, Memic F, van der Zwan J, et al
Cell 2018 08;174(4):999-1014.e22
Transcription and Signaling Regulators in Developing Neuronal Subtypes of Mouse and Human Enteric Nervous System.
Memic F, Knoflach V, Morarach K, Sadler R, Laranjeira C, Hjerling-Leffler J, et al
Gastroenterology 2018 02;154(3):624-636
Ascl1 Is Required for the Development of Specific Neuronal Subtypes in the Enteric Nervous System.
Memic F, Knoflach V, Sadler R, Tegerstedt G, Sundström E, Guillemot F, et al
J. Neurosci. 2016 Apr;36(15):4339-50
Domain-specific control of neurogenesis achieved through patterned regulation of Notch ligand expression.
Marklund U, Hansson EM, Sundström E, de Angelis MH, Przemeck GK, Lendahl U, et al
Development 2010 Feb;137(3):437-45
Identification of intrinsic determinants of midbrain dopamine neurons.
Andersson E, Tryggvason U, Deng Q, Friling S, Alekseenko Z, Robert B, et al
Cell 2006 Jan;124(2):393-405