Modeling of genetic regulatory networks in the differentiation of neural crest stem cells to sensory neurons by means of boolean networks

  • Jorge Marcelo Aráus-Patiño Universidad de los Andes
  • Helena Groot-Restrepo Universidad de los Andes
  • Andrés Fernando González-Barrios Universidad de los Andes


In the present study we have generated a GRN comprising the process by which neural crest stem cells develop to two types of sensory neurons (Propioceptors and Nocioceptors). We have also been able to find patterns of regulation (motifs) that act cooperatively to control such process. Surprisingly, these motifs take place in similar stages during the development of erythrocytes from hematopoietic stem cells. Regarding the complexity of the GRN found, we then used Random Boolean Networks (RBN) for this purpose, which showed key components as well as the dynamics of the process through changes in initial conditions. Finally, the motifs were reflected in the model, suggesting insights for further studies.
= 9 veces | PDF (ESPAÑOL (ESPAÑA))
= 4 veces|


Download data is not yet available.


S. Gilbert. Developmental Biology. 7a ed. Ed. Sinauer Associates In. Publishers. Sunderland (MA). 2006. pp. 101-137.

G. Swiers, R. Patient, M. Loose.“Genetic regulatory networks programming hematopoietic stem cells and erythroid lineage specifi cation”. Develop. Biol. Vol. 294. 2006. pp. 525-540.

W. J. R Longabaugha, E.H. Davidson, H. Bolouri. “Computational representation of developmental genetic regulatory networks”. Develop. Biol. Vol. 283. 2005. pp. 1-16.

R. Gupta,L. E. K. Achenie.“A network model for gene regulation”.

Comp. Chem. Eng. Vol 31. 2006. pp. 950- 961.

D. Wilkinson. Stochastic modeling for Systems Biology. Ed. Chapman&Hall/CRC. Boca Ratón (FL). 2006. pp. 345-370.

G. J. Hickman, P. T. Hodgman.“ Inference of genetic regulatory networks using boolean-network inference methods”. J. Bioinform. Comput. Biol. Vol 32.2005. pp. 1-7.

D. Meulemans, M. Bronner-Fraser.“Gene-Regulatory Interactions in Neural Crest Evolution and Development”. Develop. Cell. Vol 7. 2004. pp. 291- 299.

D. Raible.“Development of the neural crest: achieving specifi city in regulatory pathways”. Curr. Op. Cell. Biol. Vol 18. 2006. pp. 698-703.

C. E. Krull.“Segmental organization of neural crest migration”. Mech. Develop. Vol. 105. 2001. pp. 37-45.

Y. Morikawa, F. D’Autréaux, M. D. Gershon,P. Cserjesi. “Hand2 determines the noradrenergic phenotype in the mouse sympathetic nervous system”. Develop. Biol. Vol. 307. 2007. pp. 114-126.

N. Douarin, E. Dupin. “Multipotentiality of the neural crest”. Curr. Op. Gen. Develop. Vol 13. 2003. pp. 529- 536.

C. Paratore, G. Brugnoli, H. Y. Lye, U. Suter, L. Sommer. “The Role of the Ets Domain Transcription Factor Erm in Modulating Differentiation of Neural Crest Cells”. Develop. Biol. Vol. 250. 2002. pp. 168- 180.

L. Lo, D. J.Anderson.“Postmigratory Neural Crest Cells Expressing c-RET Display Restricted Developmental and proliferative capacities”. Neuron. Vol. 15. 1995. pp. 527-539.

S. Eng, J. Lanier, N. Fedtsova, E. Turner. “Coordinated regulation of gene expression by Brn3a in developing sensory Ganglia”. Develop. Vol. 131. 2004. pp. 3859- 3870.

D. Levanon, D. Bettoun, C. Harris Cerruti, W. E.oolf, V. Negreanu,R. Eilam, Y. Bernstein, D. Goldenberg, C. Xiao, M. Fliegauf,E. Kremer, F.Otto,O. Brenner,A. Lev-Tov, Y. Groner.“The Runx3 transcription factor regulates development and survival of TrkC dorsal root ganglia neurons”. EMBO J. Vol. 21. 13. 2002. pp. 3454-3463.

L. Ma, J. Merenmies, L. F. Parada. “Molecular characterization of the TrkA/NGF receptor minimal enhancer reveals regulation by multiple cis elements to drive embryonic neuron expression”. Develop.Vol. 127. 2000. pp. 3777-3788.

L. Ma, L. Lei, S. R. Eng, E. Turner, L. Parada. “Brn3a regulation of TrkA/NGF receptor expression in developing sensory neurons”. Develop. Vol. 130. 2003. pp. 3525-3534.

L. Lei, L. Ma, S. Nef, T. Thai,L. Parada. “mKlf7, a potential transcriptional regulator of TrkA nerve growth factor receptor expression in sensory and sympathetic neurons”. Develop. Vol. 128. 2001. pp. 1147-1158.

D. Levanona, O. Brenner, V. Negreaunu, D. Bettoun, R. Eilam, J. Lotem, U. Gat, F. Otto, N. Speck,Y. Grone.“Spatial and temporal expression pattern of Runx3 (Aml2) and Runx1 (Aml1) indicates nonredundant functions during mouse embryogenesis”. Mech. Develop. Vol. 109. 2001. pp. 413-417.

A. Wiggins, G. Wei, E. Doxakis, C. Wong, A. Tang, K. Zang, E. Luo, R. L. Neve, L. F. Reichardt, E. Huang. “Interaction of Brn3a and HIPK2 mediates transcriptional repression of sensory neuron survival”. J. Cell Biol. Vol. 167. 2004. pp. 257-267.

H. Y. Lee, M. Kleber, L. Hari, V. Brault, U. Suter, M. M. Taketo, R. Kemler, L. Sommer.“Instructive Role of Wnt/ ß-Catenin in Sensory Fate Specifi cation in Neural Crest Stem Cells”. Science. Vol. 303. 2004. pp. 1020-1023.

P. White, S. J. Morrison, K. Orimito, C. Kubu, J. Verdi, D. J. Anderson. “Neural Crest Stem Cells Undergo Cell-Intrinsic Developmental Changes in Sensitivity to Instructive Differentiation Signals”. Neuron. Vol. 29. 2001. pp. 57-71.

S. A. Kauffman. “Proposal for using the ensemble approach to understand genetic regulatory networks”. J. Theor. Biol. Vol. 230. 2004. pp. 581-590.

S. Scott. Sensory Neurons. Ed. Oxford University. New York. 1992. pp. 45-67.

G. E. Schepers, R. D. Teasdale, P. Koopman. “Twenty Pairs of Sox: Extent, homology and nomenclature of mouse and human Sox transcription factors”. Develop. Cell. Vol. 3. 2002. pp. 167-170.

How to Cite
Aráus-Patiño J. M., Groot-Restrepo H., & González-Barrios A. F. (2013). Modeling of genetic regulatory networks in the differentiation of neural crest stem cells to sensory neurons by means of boolean networks. Revista Facultad De Ingeniería Universidad De Antioquia, (58), 238-246. Retrieved from